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Correlation between inertial cavitation dose and endothelial cell damage in vivo.

Previous in vivo studies have demonstrated that vascular endothelial damage can result when vessels containing gas-based microbubble ultrasound contrast agent (UCA) are exposed to MHz-frequency pulsed ultrasound (US) of sufficient pressure amplitudes, presumably as a result of inertial cavitation (IC). The hypothesis guiding this research was that IC is the primary mechanism by which the vascular endothelium (VE) is damaged when a vessel is exposed to pulsed 1-MHz frequency US in the presence of circulating UCA. The expectation was that a correlation should exist between the magnitude and duration of IC activity and the degree of VE damage. Rabbit auricular vessels were exposed in vivo to 1.17-MHz focused US of variable peak rarefaction pressure amplitude (1, 3, 6.5 or 9 MPa), using low duty factors (0.04% or 0.4%), pulse lengths of 500 or 5000 cycles, with varying treatment durations and with or without infusion of a shelled microbubble contrast agent. A broadband passive cavitation detection system was used to measure IC activity in vivo within the targeted segment of the blood vessel. The magnitude of the detected IC activity was quantified using a previously reported measure of IC dose. Endothelial damage was assessed via scanning electron microscopy image analysis. The results supported the hypothesis and demonstrate that the magnitude of the measured IC dose correlates with the degree of VE damage when UCA is present. These results have implications for therapeutic US-induced vascular occlusion.

Albumins↗

Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumour perfusion in small animals.

Replenishment kinetics of microbubbles were adapted to a single bolus injection to investigate tumour angiogenesis in small animals with intermittent imaging, and to compare vascularisation parameters from this new approach with conventional power Doppler ultrasound (US). A reformulation of the imaging protocol and the derivation of perfusion parameters was necessary, taking into account the time-dependence of the systemic microbubble concentration after single bolus injection. Using this new method, tumour vascularisation was evaluated in 13 experimental murine tumours. Furthermore, parameters calculated with intermittent imaging after bolus injection of 100 microl Levovist were compared with parameters from the signal intensity-time curve. The results showed that quantifying tumour perfusion, blood volume and flow, as well as the assessment of the mean blood velocity (in m/s), is possible in tumours with a volume of more than 0.1 mL. In larger tumours, a lower perfusion was calculated than in smaller ones (k = -0.88; p < 0.001). Only limited correlations were found between conventional power Doppler US quantities and parameters of intermittent sonography: Perfusion correlated with the maximum signal intensity (k = 0.61, p < 0.05) and the gradient to maximum (k = 0.82, p < 0.01), full width-half maximum was associated with blood volume (k = 0.62, p < 0.05). We conclude that intermittent bolus contrast sonography allows the quantification of tumour perfusion, even in small animals, and the monitoring of basic antiangiogenic studies with perfusion parameters shows a higher significance than conventional power Doppler US.

Animals↗

Real-time perfusion imaging: a new echocardiographic technique for simultaneous evaluation of myocardial perfusion and contraction.

Myocardial contrast echocardiography (MCE) with high acoustic energy and triggered harmonic imaging is the best established ultrasound technique to date for the assessment of myocardial perfusion. With this technique, however, the ultimate goal of MCE (noninvasive real-time simultaneous assessment of myocardial perfusion and function after an intravenous injection of microbubbles) is not met. Recently, technologic advances have enabled myocardial opacification to be visualized during low-energy real-time imaging. During real-time perfusion imaging, wall motion and myocardial perfusion may be assessed simultaneously, obviating the need of the presently time-consuming combination of different imaging modalities. When high-energy ultrasound bursts are periodically transmitted to produce bubble destruction during low-power imaging, the consecutive frames after destruction delineate the restoration of contrast intensity. Microbubble replenishment rate and peak intensity may be determined subsequently, and provide reliable quantitative parameters of regional microcirculatory flow. This review will introduce the modalities used for real-time perfusion imaging with focus on power pulse inversion imaging and quantitative analysis. Furthermore, we will describe the clinical role the technique may have in the identification of coronary artery disease, quantification of coronary stenosis severity, assessment of myocardial viability, determination of infarction size, and evaluation of reflow and no- or low-reflow after acute myocardial infarction.

Contrast Media↗

Optical observations of acoustical radiation force effects on individual air bubbles.

Previous studies dealing with contrast agent microbubbles have demonstrated that ultrasound (US) can significantly influence the movement of microbubbles. In this paper, we investigated the influence of the acoustic radiation force on individual air bubbles using high-speed photography. We emphasize the effects of the US parameters (pulse length, acoustic pressure) on different bubble patterns and their consequences on the translational motion of the bubbles. A stream of uniform air bubbles with diameter ranging from 35 microm to 79 microm was generated and insonified with a single US pulse emitted at a frequency of 130 kHz. The bubble sizes have been chosen to be above, below, and at resonance. The peak acoustic pressures used in these experiments ranged from 40 kPa to 120 kPa. The axial displacements of the bubbles produced by the action of the US pulse were optically recorded using a high-speed camera at 1 kHz frame rate. The experimental results were compared to a simplified force balance theoretical model, including the action of the primary radiation force and the fluid drag force. Although the model is quite simple and does not take into account phenomena like bubble shape oscillations and added mass, the experimental findings agree with the predictions. The measured axial displacement increases quasilinearly with the burst length and the transmitted acoustic pressure. The axial displacement varies with the size and the density of the air bubbles, reaching a maximum at the resonance size of 48 microm. The predicted displacement values differ by 15% from the measured data, except for resonant bubbles for which the displacement was overestimated by about 40%. This study demonstrates that even a single US pulse produces radiation forces that are strong enough to affect the bubble position.

Acoustics↗

The effect of time and of vasoactive drugs on capillary leakage induced during myocardial contrast echocardiography.

BACKGROUND: Premature ventricular contractions (PVC), capillary leakage, and petechial hemorrhage can occur during myocardial contrast echocardiography (MCE). The effects occur as a result of the interaction of contrast agent microbubbles and the ultrasound, but the detailed etiology of the effects is not yet clear. This study tested the hypothesis that the capillary leakage results from a physiological response to injury, which might be protracted and modulated by vasoactive drugs. METHODS: Hairless rats were anesthetized and transthoracically scanned with a diagnostic ultrasound system (GE Vingmed System V) at 1.7 MHz with 1:4 triggered frames at end systole. The scan head and rats were mounted in a 37 degrees C water bath to assure free-field conditions and placement of the heart at a similar focal distance as humans. A tail vein was cannulated for injections of Optison contrast agent, vasoactive medications, and Evans Blue dye (EB). EB was injected as a marker of capillary leakage before or after scanning. RESULTS: PVCs, petechia, and capillary leakage occurred during ultrasound exposure of microbubbles in myocardium, with no effects detected in shams. The influence of the vasoactive medications propranolol and isoproterenol on the effects did not support the hypothesis. Capillary leakage occurred during and postexposure, but diminished for EB injection 20 minutes after scanning with or without isoproterenol pretreatment. CONCLUSION: MCE induced PVCs, petechia, and capillary leakage, all of which ended immediately or within 20 minutes after the examination. Contrary to the hypothesis of a physiological mechanism, the capillary leakage appears to be primarily a mechanical effect rather than a physiological response.

Animals↗

Contrast echocardiography: clinical utility for the evaluation of left ventricular systolic function.

Despite continued improvements in imaging technology, transthoracic echocardiography does not reliably provide images adequate for interpretation in all patients. In these patients, the administration of ultrasound contrast agents can markedly enhance the diagnostic utility of the test. Contrast echocardiography relies on the ultrasound detection of contrast agents composed of encapsulated microbubbles that are generally smaller than red blood cells. Intravenous administration of microbubble contrast agents results in left ventricular opacification and facilitates delineation of the endocardial border. This procedure has been shown to consistently increase the number of myocardial segments that can be interpreted, to improve accuracy of assessing regional and global left ventricular function, to decrease interinterpreter variability, to increase interpreter confidence, and to be a cost-effective strategy. Accordingly, patient selection for contrast echocardiography should be based not only on adequacy of the baseline images, but also on the clinical question being asked.

Chemistry, Pharmaceutical↗

Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography.

OBJECTIVE: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. METHODS: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CI(myo)) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CI(myo) (relative CI (RelCI)). RESULTS: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10(X/10). In normal control subjects, CI(myo) differed between the five segments (p < 0.0001), with a lower CI(myo) in deeper segments. However, RelCI did not differ significantly between segments (p = 0.083). RelCI was lower (p < 0.0001) in the 39 infarct segments (mean (SD) -18.6 (2.8) dB) than in the 55 normal segments (mean (SD) -15.1 (1.6) dB). RelCI differed more than CI(myo) between groups. CONCLUSIONS: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction.

Adult↗

Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model.

BACKGROUND: Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. METHODS AND RESULTS: Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg x kg(-1) x d(-1)) or high dose (10 mg x kg(-1) x d(-1)) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels) obtained after a 10-minute period allowing microbubble-leukocyte interactions after contrast injection exhibited a clear gradient in these groups (12+/-2 in untreated allografts, 9+/-5 in allografts treated with low-dose CsA, 6+/-3 in allografts treated with high-dose CsA, and 2+/-1 in isografts, P<0.001). The pattern of difference in SI among the groups agreed well with that in ED-1-positive cell (macrophage) count (25+/-7, 12+/-4, 5+/-3, and 1+/-0 cells per high-power field, respectively, P<0.001), which correlated with CD3-positive cell (T lymphocyte) count (33+/-5, 22+/-5, 9+/-4, and 1+/-0 cells per high-power field, respectively, P<0.001). CONCLUSIONS: Leukocyte-targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.

Acute Disease↗

Radiation-force assisted targeting facilitates ultrasonic molecular imaging.

Ultrasonic molecular imaging employs contrast agents, such as microbubbles, nanoparticles, or liposomes, coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. In this article, we show that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. We provide a theoretical evaluation of the magnitude of acoustic radiation force and show that it is possible to displace micron-sized agents physiologically relevant distances. Following this, we show in a series of experiments that acoustic radiation force can enhance the binding of targeted agents: The number of biotinylated microbubbles adherent to a synthetic vessel coated with avidin increases as much as 20-fold when acoustic radiation force is applied; the adhesion of contrast agents targeted to alpha(v)beta3 expressed on human umbilical vein endothelial cells increases 27-fold within a mimetic vessel when radiation force is applied; and finally, the image signal-to-noise ratio in a phantom vessel increases up to 25 dB using a combination of radiation force and a targeted contrast agent, over use of a targeted contrast agent alone.

Avidin↗

Real-time excitation-enhanced ultrasound contrast imaging.

A new nonlinear contrast specific imaging modality, excitation-enhanced imaging (EEI) has been implemented on commercially-available scanners for real-time imaging. This novel technique employs two acoustic fields: a low-frequency, high-intensity ultrasound field (the excitation field) to actively condition contrast microbubbles, and a second lower-intensity regular imaging field applied shortly afterwards to detect enhanced contrast scattering. A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) with a 3.5C curved linear array and an AN2300 digital ultrasound engine (Analogic Corporation, Peabody, MA) with a P4-2 phased array transducer (Philips Medical Systems, Bothell, WA) were modified to perform EEI on a vector-by-vector basis in fundamental and pulse inversion harmonic grayscale modes. Ultrasound contrast microbubbles within an 8 mm vessel embedded in a tissue-mimicking flow phantom (ATS Laboratories, Bridgeport, CT) were imaged in vitro. While video intensities of scattered signals from the surrounding tissue were unchanged, video intensities of echoes from contrast bubbles within the vessel were markedly enhanced. The maximum enhancement achieved was 10.4 dB in harmonic mode (mean enhancement: 6.3 dB; p = 0.0007). In conclusion, EEI may improve the sensitivity of ultrasound contrast imaging, but further work is required to assess the in vivo potential of this new technique.

Albumins↗

The role of ultrasound in molecular imaging.

Ultrasound has received less attention than other imaging modalities for molecular imaging, but has a number of potential advantages. It is cheap, widely available and portable. Using Doppler methods, flow information can be obtained easily and non-invasively. It is arguably the most physiological modality, able to image structure and function with less sedation than other modalities. This means that function is minimally disturbed, and multiple repeat studies or the effect of interventions can easily be assessed. High frame rates of over 200 frames a second are achievable on current commercial systems, allowing for convenient cardiac studies in small animals. It can be used to guide interventional or invasive studies, such as needle placement. Ultrasound is also unique in being both an imaging and therapeutic tool and its value in gene therapy has received much recent interest. Ultrasound biomicroscopy has been used for in utero imaging and can guide injection of virus and cells. Ultrahigh frequency ultrasound can be used to determine cell mechanical properties. The development of microbubble contrast agents has opened many new opportunities, including new functional imaging methods, the ability to image capillary flow and the possibility of molecular targeting using labelled microbubbles.

Animals↗

Cardiovascular bubble dynamics.

Gas bubbles can form in the cardiovascular system as a result of patho-physiological conditions or can be intentionally introduced for diagnostic or therapeutic reasons. The dynamic behavior of these bubbles is caused by a variety of mechanisms, such as inertia, pressure, interfacial tension, viscosity, and gravity. We review recent advances in the fundamental mechanics and applications of cardiovascular bubbles, including air embolism, ultrasound contrast agents, targeted microbubbles for drug delivery and molecular imaging, cavitation-induced tissue erosion for ultrasonic surgery, microbubble-induced angiogenesis and arteriogenesis, and gas embolotherapy.

Animals↗

Myocardial contrast echocardiography: Role in clinical cardiology.

Recent updates in the field of echocardiography have resulted in improvements in both image quality and techniques allowing echocardiography to maintain its position as the primary non-invasive imaging modality. In particular, the development of new ultrasound contrast agents and imaging techniques have now made possible the assessment of myocardial perfusion. Myocardial contrast echocardiography utilises acoustically active gas filled microspheres (microbubbles), which have rheology similar to that of red blood cells. The detection of myocardial perfusion during echocardiographic examinations permits simultaneous assessment of global and regional myocardial structure, function, and perfusion, enabling the optimal non-invasive assessment of coronary artery disease. Myocardial contrast echocardiography is equally adept in assessing chronic coronary artery disease as well as acute coronary syndromes. Furthermore, its use is not limited solely to diagnostic assessment. Preliminary evidence suggests that targeted microbubbles may be useful in enhancing delivery of genes / drugs and in clot lysis.

Animals↗

Assessment of skeletal muscle perfusion using contrast-enhanced ultrasonography.

OBJECTIVE: The purpose of this study was to develop a clinically applicable examination method to assess perfusion of the skeletal muscle using contrast-enhanced ultrasonography (CEUS) analyzing replenishment kinetics of microbubbles. METHODS: Power Doppler sonography (7 MHz) after intravenous bolus injection of 10 mL of a microbubble contrast agent was used to repeatedly examine the perfusion of the right biceps muscle at rest and after defined exercise in 10 healthy volunteers. Parameters of perfusion, such as local blood volume, blood flow velocity, and perfusion, were calculated by a modified analysis of replenishment kinetics. For validation, CEUS was correlated with venous occlusion plethysmography (VOP) examining the right forearm flexor muscles at rest and after defined exercise. RESULTS: The CEUS examination was easily feasible and was able to depict the physiologic large variability of the right biceps muscle perfusion at rest (mean +/- SD, 3.0 +/- 2.3 [approximately mL/s x 100 mg]) compared with the results after exercise (22.9 +/- 11.0 [approximately mL/s x 100 mg]). The perfusion calculated with VOP significantly correlated with the CEUS parameters perfusion (r = 0.81; P < .001) and blood volume (r = 0.82; P < .001). The calculated mean blood flow velocity in the right forearm flexor muscles raised from 0.41 +/- 0.24 mm/s at rest to 0.64 +/- 0.39 mm/s after exercise, showing a significant correlation with the CEUS perfusion (r = 0.72; P < .001). CONCLUSIONS: Muscle perfusion can be easily and quantitatively assessed with CEUS. Compared with VOP, CEUS allows for a separate analysis of different muscle groups, unaffected by skin perfusion. Its application may be of particular interest in the diagnosis and monitoring of pathologic microvascularization in myositis or diabetic obstructive disease.

Arm↗

Ultrasonographic contrast media: has the time come in obstetrics and gynecology?

OBJECTIVE: The aim of this work was to review the technical aspects and clinical applications of contrast media (microbubbles and nanomolecular agents) in obstetric and gynecologic ultrasonographic imaging. METHODS: With the use of a computerized database (MEDLINE) and several Web-based search engines (Google Scholar and Copernic), relevant articles on ultrasonographic contrast media were reviewed. References cited in these articles and not obtained via the search engines were also reviewed. RESULTS: Ultrasonographic contrast media constitute a new and expanding technology. They are frequently used, for example, in adult cardiology. Extensive research in laboratory setups, animals, and human subjects has shown their safety and huge potential as an adjunctive tool in clinical practice. They increase signals returning from insonated tissues and are particularly effective as intravascular agents, enhancing color and Doppler signals, for instance. Preliminary results in tumor imaging are encouraging. The ultrasonographic contrast media permit pharmacokinetic perfusion studies, which may be of enormous clinical importance in the study of early cancer development. Targeted imaging and therapies are becoming a reality. Microbubbles have already brought a new dimension to diagnostic ultrasonographic imaging. Many authors have described the clinical value of these agents in liver, prostate, and breast imaging, among others. Newer types of media, the nanomolecules, are now emerging as the latest in imaging enhancers as well as therapeutic agent carriers. CONCLUSIONS: Although showing potential in imaging of the uterus and fallopian tubes as well as some obstetric applications, the contrast media, in particular the nanomolecules, seem to be most promising in ovarian cancer.

Contrast Media↗

The effects of Levovist and DD-723 in activating platelets and damaging hepatic cells of rats.

OBJECTIVE: The purpose of this study was to compare platelet activation and hepatic cell damage produced by 2 ultrasonographic contrast agents with flow cytometric and ultrastructural analysis. METHODS: Suspension samples were made by mixing Levovist (SH U508A; Schering AG, Berlin, Germany) or DD-723 (Nycomed; Amersham Health, Princeton, NJ) with whole blood. The final concentrations of Levovist in citrated whole blood were 0, 15, and 75 mg/mL, and those of DD-723 were 0, 5, and 50 microL/mL. After exposure to ultrasound in vitro, flow cytometric analysis was performed to determine the concentration of the CD62P activation-specific antigen. To compare the hepatic cell damage associated with these 2 agents, we divided 15 rats into 5 groups as follows: group 1, sham operation; group 2, Levovist injection only; group 3, DD-723 injection only; group 4, Levovist injection (contrast agent) and ultrasound exposure; and group 5, DD-723 injection and ultrasound exposure. The ultrasonographic contrast agents Levovist and DD-723 were administered through the femoral vein and sonicated continuously for the first minute; this was followed by sweeping for 5 minutes 10 seconds after the contrast agent was injected. The rats were perfused via the heart with a fixative solution immediately after the sweeping, and then the liver was excised; the specimens were studied with electron and light microscopy. RESULTS: The percentage of CD62P-expressing platelets increased in both contrast agent-ultrasound exposure groups, and the percentage of CD62P-expressing platelets was greater in the Levovist group. We observed vacuolation and round deposits in the hepatocytes in both contrast agent-ultrasound exposure groups. Microbubbles were observed in the rat Kupffer cells, and a few hepatocytes were seen unexpectedly in the DD-723 group but were found in neither the Kupffer cells nor the hepatocytes in the Levovist group. CONCLUSIONS: Both contrast agents, Levovist and DD-723, produced platelet activation and structural change in the rat hepatic cells, but only the microbubbles of DD-723 were taken up by the Kupffer cells and a few hepatocytes.

Animals↗

Detection of cardiac right-to-left shunts by contrast-enhanced harmonic carotid duplex sonography.

OBJECTIVE: Paradoxical embolization by cardiac right-to-left shunts (RLS) is increasingly recognized as an important factor for embolic stroke. Contrast-enhanced transcranial Doppler sonography (ce-TCDS) is an established diagnostic tool for RLS detection but is frequently limited because of an inadequate temporal acoustic bone window. The purpose of this study was to determine whether extracranial sonography (ECS) using harmonic frequencies improves detection of RLS. METHODS: Extracranial color duplex sonography using harmonic frequencies enables visualization of even single ultrasound contrast agent microbubbles because of oscillation. Patients with stroke and positive RLS findings on transesophageal echocardiography underwent a simultaneous extracranial and transcranial sonographic examination of the proximal common carotid artery (CCA) and middle cerebral artery (MCA) on the same side. A Valsalva strain was performed for 10 seconds after intravenous bolus injection of a galactose-based nontranspulmonary contrast agent. The B-mode frame sequences of the transverse plane of the CCA obtained by harmonic ECS and the ce-TCDS recordings of high-intensity transient signals from the MCA were analyzed offline. RESULTS: In all patients with RLS, the shunts could be identified by harmonic ECS. A close correlation could be seen between the count of visualized microbubbles in the CCA and the number of high-intensity transient signals detected on ce-TCDS in the ipsilateral MCA. CONCLUSIONS: The results of this study indicate that contrast-enhanced ultrasound harmonic imaging of the CCA using a Valsalva strain might be an optional screening tool for detection of cardiac RLS in patients with insufficient acoustic bone windows.

Carotid Artery, Internal↗

Reliability of semiquantitative ultrasonic perfusion imaging of the brain.

BACKGROUND AND PURPOSE: Contrast burst depletion imaging (CODIM) visualizes cerebral perfusion by destruction of microbubbles and observation of image intensity course. Because of its complexity, artifacts occur. Criteria of reliability to improve diagnostic significance were created and validated. METHODS AND RESULTS: Eighteen healthy volunteers were examined with 2 echo contrast agents (ECAs) and 3 frame rates in 3 regions of interest (ROIs). Perfusion coefficient (PC), Tmin (time to decrease intensity to 10% of its max), and relative error (RE) (deviation of measured data from fitted model) were determined. PC differed significantly neither between CA nor between frame rates (overall mean = 1.60 +/- 0.21 x 10(-2) s-1). Tmin differed significantly between frame rate groups (P < .001, 33.4 +/- 11.2 s/0.5 Hz; 3.6 +/- 2.5 s/5 Hz) since it is related to destruction of microbubbles that occurs with each frame and to the perfusion rate. RE was higher in the Optison group and tended to decrease in ROIs closer to the probe. CONCLUSIONS: PC was independent of frame rate and ECA. Tmin was shorter with higher frame rates. Due to a very rapid decay at 5 Hz, the ideal frame rate should be about 1 Hz, that is, because the number of frames acquired within Tmin and therefore signal-to-noise ratio is higher at 1 Hz. Since the algorithm is complex (high RE) and more artifacts should occur in patients (insufficient bone window, etc), a triggering of the insonations by, for example, heart rate could decrease artifacts and increase diagnostic power of CODIM.

Adult↗