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PubMed1997

Simultaneous bilateral contrast transcranial doppler monitoring in patients with intracardiac and intrapulmonary shunts.

The prevalence of a right-to-left intracardiac shunt, demonstrated by echocardiography and transcranial Doppler sonography has been shown to be higher in stroke patients than in normal controls. The aim of this study was to assess the sensitivity and specificity of contrast transcranial Doppler sonography in comparison to transesophageal echocardiography in the detection and differentiation of intracardiac and intrapulmonary shunts and to correlate the transcranial Doppler findings with clinical outcome and morphological findings. Forty five consecutive stroke patients with suspected paradoxical embolism were entered into the study. In all 25 patients with middle cerebral artery stroke of the left (56%) or right (44%) territory and echocardiographic demonstrated patent foramen ovale (80%) or intrapulmonary shunt (20%), simultaneous bilateral transcranial Doppler sonography of the middle cerebral arteries was performed after contrast medium injection during rest and valsalva straining under standardized and optimized conditions. Overall sensitivity for the detection of a right-to-left shunt by contrast transcranial Doppler sonography was 97% and overall specificity was 70%. Bilateral appearance of microbubbles, microbubble count and time delay of microbubble appearance significantly increased after valsalva straining. In patients with intracardiac shunts, a significantly higher microbubble count (32 vs. 13 in patients with an intrapulmonary shunt) and a shorter time interval of microbubble appearance (11 vs. 14 s in patients with intrapulmonary shunts) was observed. There was no correlation between the side and numerical distribution of microbubble count and the location and severity of the current clinical symptoms, as well as between microbubble count and presence and hemispherical distribution of brain infarcts. Transcranial Doppler sonography is a highly sensitive method for the detection of right-to-left shunts, whether of cardiac or pulmonary location. However. no correlation was found between the side and number of microbubbles counted and the clinical symptomatology.

Adolescent↗

PubMed1998

Spontaneous redistribution after reperfusion: a unique property of AIP 201, an ultrasound contrast agent.

OBJECTIVES: We sought to determine the mechanism of spontaneous redistribution of AIP 201 microbubbles after reperfusion from a single left heart injection performed during coronary occlusion. BACKGROUND: AIP 201, an ultrasound contrast agent consisting of 10-microm sized microbubbles, has demonstrated spontaneous myocardial redistribution in preliminary studies. METHODS: Myocardial video intensity (VI) and radiolabeled microsphere-derived myocardial blood flow (MBF) were measured serially after reperfusion in seven dogs undergoing an AIP 201 injection during coronary occlusion. The behavior of these bubbles was also assessed in the rat spinotrapezius muscle using intravital microscopy (IM), both with and without ultrasound. The effect of ultrasound on these bubbles was also determined in vitro. RESULTS: A spontaneous and gradual increase in myocardial VI was noted after reperfusion, which was related to the magnitude of increase in MBF to that region (r=0.82, p < 0.001). On IM, most of the microbubbles were seen entrapped in small arterioles. Some larger arterioles had aggregates of microbubbles that periodically became dislodged and moved downstream. This behavior was not affected in vivo by ultrasound. In vitro, however, microbubble aggregation was noted only during ultrasound exposure. CONCLUSIONS: The magnitude of redistribution of AIP 201 microbubbles to the reperfused myocardium is related to changes in MBF and occurs from their dislodgement from microbubble aggregates entrapped in large arterioles. In vitro microbubble aggregation seen during ultrasound exposure was not reproduced in vivo. These results may have important implications for studying the effects of interventions in acute coronary syndromes and after coronary artery bypass graft surgery.

Animals↗

PubMedDate not supplied

A review of nonconventional ultrasound techniques and contrast-enhanced ultrasonography of noncardiac canine disorders.

Modern ultrasound contrast media are gas-containing stabilized microbubbles that remain intact in the circulating blood for several minutes after intravenous injection and increase the intensity of the backscattered ultrasound. When the microbubbles disappear from the blood, they can be detected in the parenchyma of the liver and the spleen for about 30 more minutes (late liver- and spleen-specific phase). The insonated microbubbles produce second harmonic ultrasound frequencies, whose detection requires nonconventional ultrasound modalities such as pulsed inversion imaging. Nonconventional ultrasound techniques can also be used without microbubbles because second harmonics can be generated by ultrasound in tissues as well. The physical principles and advantages of nonconventional ultrasound techniques are described. The circulating microbubbles can be used not only to enhance weak Doppler signals, but also to perform dynamic contrast studies. Contrast-enhanced dynamic ultrasound studies--similar to contrast-enhanced CT and MRI examinations--have been used in humans to characterize lesions noninvasively (i.e., without biopsies) found during conventional ultrasound examinations. To map the distribution of contrast medium in a nodule or in an organ, specific scanning techniques such as stimulated acoustic emission have been developed. Stimulated acoustic emission occurs when high acoustic pressure ultrasonic waves disrupt the stationary or slowly moving microbubbles. This results in the release of a large amount of harmonic ultrasound frequencies. When the stimulated acoustic emission technique is used for dynamic studies, scanning must be interrupted several times to allow the microvasculature of the lesion to refill with microbubbles (interval delay imaging). The contrast patterns of malignant and benign hepatic nodules in humans have been the most intensively studied. Another type of dynamic study in humans measures the transit time of the contrast medium; that is, how fast the peripherally injected microbubbles reach the hepatic veins. Hepatic cirrhosis can be differentiated from other diffuse parenchymal liver diseases by a shorter transit time. Introducing nonconventional ultrasound techniques and ultrasound contrast media in veterinary diagnostic imaging may have potential value; however, intensive research should be carried out before ultrasound contrast agents can routinely be used in clinical practice.

Animals↗

PubMedDate not supplied

Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow.

Targeted ultrasound contrast materials (gas-filled microbubbles carrying ligands to endothelial selectins or integrins) have been investigated as potential molecular imaging agents. Such microbubbles normally exhibit good targeting capability at the slower flow conditions. However, in the conditions of vigorous flow, binding may be limited. Here, we describe a microbubble capable of efficient binding to targets both in slow and fast flow (exceeding 4 dyne/cm(2) wall shear stress) using a clustered polymeric form of the fast-binding selectin ligand sialyl Lewis(X). Microbubbles were prepared from decafluorobutane gas and stabilized with a monolayer of phosphatidylcholine, PEG stearate and biotin-PEG-lipid. Biotinylated PSLe(x) (sialyl Lewis(X) polyacrylamide) or biotinylated anti-P-selectin antibody (RB40.34) was attached to microbubbles via a streptavidin bridge. In a parallel plate flow chamber targeted adhesion model, PSLe(x) bubbles demonstrated specific adhesion, retention and slow rolling on P-selectin-coated plates. Efficiency of firm targeted adhesion to a P-selectin surface (140 molecules/microm(2)) was comparable for antibody-carrying bubbles and PSLe(x)-targeted bubbles at 0.68 dyne/cm(2) shear stress. At fast flow (4.45 dyne/cm(2)), PSLe(x)-targeted bubbles maintained their ability to bind, while antibody-mediated targeting dropped more than 20-fold. At lower surface density of P-selectin (7 molecules/microm(2)), targeting via PSLe(x) was more efficient than via antibody under all the flow conditions tested. Negative control casein-coated plates did not retain bubbles in the range of flow conditions studied. To confirm echogenicity, targeted PSLe(x)-bubbles were visualized on P-selectin-coated polystyrene plates by ultrasound imaging with a clinical scanner operated in pulse inversion mode; control plates lacking targeted bubbles did not show significant acoustic backscatter. In vivo, in a murine model of inflammation in the femoral vein setting, targeting efficacy of intravenously administered PSLe(x)-microbubbles was comparable with targeting mediated by anti-P-selectin antibody, and significantly exceeded the accumulation of non-targeted control bubbles. In the inflamed femoral artery setting, PSLe(x)-mediated microbubble targeting was superior to antibody-mediated targeting.

Acrylic Resins↗

PubMed2006

Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

Adenoviridae↗

PubMed2006

Ultrasound contrast agents: an overview.

With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI<0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating vasospasm after subarachnoid haemorrhage). An important situation where demonstrating tissue devitalisation is important is in interstitial ablation of focal liver lesions: using microbubble contrast agents at the end of a procedure allows immediate evaluation of the adequacy of the ablation which can be extended if needed; this is much more convenient and cost-saving than moving the patient to CT and perhaps needing an additional ablation session at a later date. Similar considerations suggest that contrast-enhanced ultrasound might have a role in abdominal trauma: injury to the liver, spleen and kidneys can be assessed rapidly and repeatedly if necessary. Its role here alongside dynamic CT remains to be evaluated. Infarcts or ischaemia and regions of abnormal vascularity, especially in malignancies, in the kidneys and spleen seem to be useful and improved detection of the neovascularisation of ovarian carcinomas is promising. Similar benefits in the head-and-neck and in the skin while the demonstration of the neovascularisation of atheromatous plaques and of aggressive joint inflammation offer interesting potentials.

Contrast Media↗

PubMed2006

Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system.

Rayleigh-Plesset analysis, ultra-high speed photography, and single bubble acoustical recordings previously were applied independently to characterize the radial oscillation and resulting echoes from a microbubble in response to an ultrasonic pulse. In addition, high-speed photography has shown that microbubbles are destroyed over a single pulse or pulse train by diffusion and fragmentation. In order to develop a single model to characterize microbubble echoes based on oscillatory and destructive characteristics, an optical-acoustical system was developed to simultaneously record the optical image and backscattered echo from each microbubble. Combined observation provides the opportunity to compare predictions for oscillation and echoes with experimental results and identify discrepancies due to diffusion or fragmentation. Optimization of agents and insonating pulse parameters may be facilitated with this system. The mean correlation of the predicted and experimental radius-time curves and echoes exceeds 0.7 for the parameters studied here. An important application of this new system is to record and analyze microbubble response to a long pulse in which diffusion is shown to occur over the pulse duration. The microbubble response to an increasing or decreasing chirp is evaluated using this new tool. For chirp insonation beginning with the lower center frequency, low-frequency modulation of the oscillation envelope was obvious. However, low-frequency modulation was not observed in the radial oscillation produced by decreasing chirp insonation. Comparison of the echoes from similar sized microbubbles following increasing and decreasing chirp insonation demonstrated that the echoes were not time-reversed replicas. Using a transmission pressure of 620 kPa, the -6 dB echo length was 0.9 and 1.1 micros for increasing and decreasing chirp insonation, respectively (P = 0.02). The mean power in the low-frequency portion of the echoes was 8 (mV)2 and 13 (mV)2 for increasing and decreasing chirp insonation, respectively (P = 0.01).

Acoustics↗

PubMed2002

Evolving applications for contrast ultrasound.

Future clinical applications for contrast-enhanced ultrasound will likely expand beyond perfusion imaging. There has been considerable progress in the past few years in the development of site-targeted microbubbles, such that instead of passing unimpeded through the circulation, they attach to specific markers of disease. Accumulation of targeted microbubbles in diseased tissue can allow noninvasive ultrasound imaging of molecular and cellular processes. In this review, the strategies for designing site-targeted microbubbles and the early experience with molecular imaging will be discussed. The use of microbubbles and ultrasound for therapeutic purposes is also just now being realized. A promising development is the ability to package either drugs or genes into or onto microbubble contrast agents. Conceptually, ultrasound-mediated destruction of microbubble vehicles will provide focal release in a tissue of interest and may facilitate extravascular sojourn of the therapeutic agent. Preliminary experience using microbubbles as vectors for gene delivery is also reviewed.

Antibodies, Monoclonal↗

PubMed1998

In vitro studies of a new thrombus-specific ultrasound contrast agent.

Ultrasound is used as a primary diagnostic technique for the detection of deep venous thrombosis. The purpose of this study is to describe the development of a new thrombus-specific ultrasound contrast agent: The linear hexapeptide (lysine-glutamine-alanine-glycine-aspartate-valine) was synthesized and coupled to a lipid moiety. The targeted lipid was then incorporated into the lipid blend for the contrast agent Aerosomes (ImaRx, Tucson, AZ, USA). The lipid blend was used to entrap perfluorobutane microbubbles. The microbubbles were sized and studied in vitro for acoustic stability, binding to blood clot, and ultrasound enhancement in vitro of blood clot. The results showed the mean size of the specific ultrasound contrast agent (MRX-408) was about 2.0 microm. The microbubbles appeared as smooth spherical structures. Microscopy showed that the targeted bubbles bound to blood clot whereas control, nontargeted bubbles did not bind to blood clot. In vitro acoustic study showed similar stability of the microbubbles compared with control microbubbles. The targeted microbubbles enhanced blood clot in vitro whereas nontargeted microbubbles did not enhance clot. Thus this promising new thrombus-specific ultrasound contrast agent could potentially improve detection of thrombosis by ultrasound and might be useful for distinguishing between new and old thrombosis. In vivo studies are in progress.

Contrast Media↗

PubMedDate not supplied

Attenuation deforms time-intensity curves during contrast echocardiography: implications for assessment of mean transit rates.

The mean transit rate of microbubbles of air obtained from time-intensity curves during contrast echocardiography can be used to evaluate flow through a vascular system, provided the volume of distribution of the system remains constant. We hypothesized that attenuation commonly associated with contrast echocardiography distorts the time-intensity curves, producing an error in the estimation of the mean transit rate of the microbubbles. The purpose of this study was to characterize this distortion with computer simulations and to study the effect of attenuation on the estimation of mean transit rate in an in vitro experiment. We also sought to determine if removing the data points from the time-intensity plots that visually can be attributed to attenuation before curve fitting can minimize the error in the estimation of mean microbubble transit rate. In both computer simulations and experimentally acquired in vitro data, attenuation distorted the time-intensity curves, producing an underestimation of mean microbubble transit rates. The mean microbubble transit rate decreased with an increase in microbubble concentration. Removing the points that visually were attributed to attenuation before curve fitting did not correct this error completely in the computer-simulated data and failed to correct it at all in the experimental data. These results have major practical implications in assessing mean microbubble transit rates during contrast echocardiography.

Albumins↗

PubMed2001

Delivery of drugs with ultrasound.

In this article we discuss the potential role of microbubbles, traditionally used as ultrasound contrast agents, for site-specific drug delivery. To reach this goal, microbubbles capable of carrying a drug payload are being developed. To ensure that these microbubbles reach sufficient local concentration at disease sites, specific targeting for diseased tissues can be accomplished using several strategies. These strategies rely on either the intrinsic properties of microbubble shells or conjugation of monoclonal antibodies or other ligands to these shells that recognize antigens expressed in regions of disease. Site-specific delivery of antiinflammatory, antineoplastic, and thrombolytic drugs with microbubbles can be further enhanced by the ability to locally destroy microbubbles within an acoustic field, thereby releasing drugs and improving drug efficacy without systemic adverse effects. In the case of thrombi, ultrasound-mediated microbubble destruction also may facilitate the process of clot lysis. This review also will consider current limitations and technological advances required for the development of this field.

Contrast Media↗

PubMedDate not supplied

Assessment of inflammation with contrast ultrasound.

Future clinical applications of contrast-enhanced ultrasound will likely expand beyond the assessment of microvascular perfusion. One promising direction is the development of site-targeted microbubbles that are retained within regions of a specific disease process and thereby allow phenotypic characterization of tissue. Inflammation is an ideal disease state for targeting with microbubbles because the pathophysiologic processes that initiate and support the inflammatory response occur within the microcirculation, where microbubbles reside. This review describes methods that have been used to direct microbubbles to regions of inflammation. These methods rely on either (1) intrinsic properties of albumin or lipid microbubbles that promote their attachment to leukocyte adhesion molecules, or (2) conjugation of monoclonal antibodies or other ligands to the microbubble surface that recognize specific endothelial cell adhesion molecules. This review also considers ultrasound imaging methods that may be used to detect microbubbles retained within inflamed tissue.

Cell Adhesion Molecules↗

PubMed2006

Transcranial Doppler detection of microembolic signals during pulmonary vein antrum isolation: implications for titration of radiofrequency energy.

BACKGROUND: Cerebrovascular events are an important complication during pulmonary vein antrum isolation (PVAI). Microembolic signals (MES) have been associated with stroke and neurological impairment. However, the incidence of MES during PVAI, and their relationship to microbubble formation and radiofrequency (RF) parameters are unknown. OBJECTIVES: We sought to assess the relationship between MES, microbubble detection, and neurological outcome and the impact of RF titration strategy on these parameters. METHODS: We studied 202 patients in two groups undergoing PVAI using an intracardiac echocardiography (ICE)-guided technique. MES were detected by transcranial Doppler (TCD) using insonation of the middle cerebral arteries. The number of microbubbles on ICE were qualitatively labeled as FEW, MODERATE, and SHOWER. In group I (n = 107), RF output was titrated to avoid microbubble formation and in group II (n = 95), standard power-limited RF output was used. RESULTS: TCD detected MES in all 202 patients during PVAI with an average of 1,793 +/- 547 per patient; 90% were detected during left atrial ablation. Over 85% of MES occurred after microbubbles. Group I patients had significantly lower numbers of MES (1,015 +/- 438 per patient) compared to group II patients (2,250 +/- 864 per patient) (P < 0.05). Group II also had a 3.1% incidence of acute neurological complications versus 0.9% in group I (P = 0.10). Patients with clinical events had significantly higher numbers of MES. There were no significant correlations between RF power, temperature, or impedence and MES number. CONCLUSIONS: MES directly correlate to the amount of microbubble formation on ICE, and may result in cerebroembolic complications. Titration of RF according to microbubble formation by ICE during PVAI may be important for minimizing the occurrence of MES and possibly acute neurological complications.

Atrial Fibrillation↗

PubMed1999

Imaging of Myocardial Perfusion with SonoVuetrade mark in Patients with a Prior Myocardial Infarction.

Myocardial contrast echocardiography (MCE) is an evolving noninvasive imaging technique that can be used to assess regional myocardial perfusion. MCE relies upon the detection of nonlinear ultrasound signal from gas-filled microbubbles during their microvascular transit, resulting in tissue opacification. Provided that the relation between myocardial microbubble concentration and video intensity (VI) is within the linear range, VI measured from any myocardial region reflects the relative tissue concentration of microbubbles, which is influenced by three factors: (1) microbubble concentration in blood; (2) the myocardial blood volume fraction; and (3) microbubble destruction that occurs within the ultrasound beam. In this article, we discuss how these three factors may influence myocardial perfusion information provided by MCE and highlight the importance of image processing. In order to illustrate these concepts, we examine data obtained during perfusion imaging in patients with prior myocardial infarction using intermittent harmonic imaging at various ultrasound pulsing intervals (PIs) during bolus and continuous venous infusions of a second-generation microbubble agent (SonoVue(trade mark)). Our results suggest that evaluation of resting perfusion is most accurate when both myocardial blood volume and blood velocity are assessed. This information is provided only with continuous infusions of microbubbles during imaging protocols that vary the ultrasound PI.

Journal Article↗

PubMed2006

Nitric oxide delivery by ultrasonic cracking: some limitations.

Nitric oxide (NO) has been implicated in smooth muscle relaxation. Its use has been widespread in cardiology. Due to the effective scavenging of NO by hemoglobin, however, the drug has to be applied locally or in large quantities, to have the effect desired. We propose the use of encapsulated microbubbles that act as a vehicle to carry the gas to a region of interest. By applying a burst of high-amplitude ultrasound, the shell encapsulating the gas can be cracked. Consequently, the gas is released upon which its dissolution and diffusion begins. This process is generally referred to as (ultra)sonic cracking. To test if the quantities of released gas are high enough to allow for NO-delivery in small vessels (ø<200 microm), we analyzed high-speed optical recordings of insonified stiff-shelled microbubbles. These microbubbles were subjected to ultrasonic cracking using 0.5 or 1.7 MHz ultrasound with mechanical index MI>0.6. The mean quantity released from a single microbubble is 1.7 fmol. This is already more than the NO production of a 1mm long vessel with a 50 microm diameter during 100 ms. However, we simulated that the dissolution time of typical released NO microbubbles is equal to the half-life time of NO in whole blood due to scavenging by hemoglobin (1.8 ms), but much smaller than the extravascular half-life time of NO (>90 ms). We conclude that ultrasonic cracking can only be a successful means for nitric oxide delivery, if the gas is released in or near the red blood cell-free plasma next to the endothelium. A complicating factor in the in vivo situation is the variation in blood pressure. Although our simulations and acoustic measurements demonstrate that the dissolution speed of free gas increases with the hydrostatic pressure, the in vitro acoustic amplitudes suggest that the number of released microbubbles decreases at higher hydrostatic pressures. This indicates that ultrasonic cracking mostly occurs during the expansion phase.

Capsules↗

PubMed2004

Vascular flow and perfusion imaging with ultrasound contrast agents.

Current techniques for imaging ultrasound (US) contrast agents (UCA) make no distinction between low-velocity microbubbles in the microcirculation and higher-velocity microbubbles in the larger vasculature. A combination of radiofrequency (RF) and Doppler filtering on a low mechanical index (MI) pulse inversion acquisition is presented that differentiates low-velocity microbubbles (on the order of mm/s) associated with perfusion, from the higher-velocity microbubbles (on the order of cm/s) in larger vessels. In vitro experiments demonstrate the ability to separate vascular flow using both harmonic and fundamental Doppler signals. Fundamental and harmonic Doppler signals from microbubbles using a low-MI pulse-inversion acquisition are compared with conventional color Doppler signals in vivo. Due to the lower transmit amplitude and enhanced backscatter from microbubbles, the in vivo signal to clutter ratios for both the fundamental (-11 dB) and harmonic (-4 dB) vascular flow signals were greater than with conventional power Doppler (-51 dB) without contrast agent. The processing investigated here, in parallel with conventional pulse-inversion processing, enables the simultaneous display of both perfusion and vascular flow. In vivo results demonstrating the feasibility and potential utility of the real-time display of both perfusion and vascular flow using US contrast agents are presented and discussed.

Algorithms↗

PubMed2001

Quantification of renal blood flow with contrast-enhanced ultrasound.

OBJECTIVES: The goal of this study was to determine the ability of contrast-enhanced ultrasound (CEU) to quantify renal tissue perfusion. BACKGROUND: The kinetics of tracers used to assess renal perfusion are often complicated by countercurrent exchange, tubular transport or glomerular filtration. We hypothesized that, because gas-filled microbubbles are pure intravascular tracers with a rheology similar to that of red blood cells, CEU could be used to quantify renal tissue perfusion. METHODS: During a continuous venous infusion of microbubbles (SonoVue), regional renal perfusion was quantified in nine dogs using CEU by destroying microbubbles and measuring their tissue replenishment with intermittent harmonic imaging. Both renal blood volume fraction and microbubble velocity were derived from pulsing-interval versus video-intensity plots. The product of the two was used to calculate renal nutrient blood flow. Renal arterial blood flow was independently measured with ultrasonic flow probes placed directly on the renal artery and was increased using dopamine and decreased by placement of a renal artery stenosis. RESULTS: An excellent correlation was found between cortical nutrient blood flow using microbubbles and ultrasonic flow probe-derived renal blood flow (r = 0.82, p < 0.001) over a wide range (2.5 fold) of flows. CONCLUSIONS: Ultrasound examination during microbubble infusion can be used to quantify total organ as well as regional nutrient blood flow to the kidney.

Animals↗

PubMedDate not supplied

Sonicated echocardiographic contrast agents: reproducibility studies.

This article describes the production, analysis, and reproducibility of forming microbubbles for contrast ultrasound imaging. The sonication method used to generate microbubbles was tested by four independent observers, and a subsequent laser particle counter analysis of microbubble size and concentration determined the reproducibility of the method. The results indicated that the mean bubble size was 3.3 +/- 1.2 microns for the entire group, based on three trials of each of the four participants. The characteristics of the bubble size of the microbubbles between observers were assessed with a Poisson distribution with the reproducibility based on the sample mean for each observer's trials. Standardization and calibration of the laser particle counter was accomplished with commercially available latex spheres, sonicated albumin microspheres, and a Coulter counter analysis. Our results indicate that the sonication technique generates small microbubbles with a reproducible uniform size distribution. The method of microbubble production is reproducible and can be widely applied for use in contrast echocardiographic perfusion imaging of tissue in a variety of research and clinical studies.

Air↗