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PubMed2003

Carotid arteries: contrast-enhanced US angiography--preliminary clinical experience.

B-mode ultrasonographic (US) angiography enhanced with a microbubble-based US contrast agent (FS069) was evaluated in human subjects with carotid artery disease. Results at contrast material-enhanced US angiography and duplex US were compared with those at conventional angiography. Both US angiography and duplex US accurately depicted stenoses of 70% or more compared with those depicted at conventional angiography. The percentage diameter stenosis of the internal carotid artery measured at US angiography strongly correlated with that measured at conventional angiography (r = 0.988). The percentage area stenosis measured at US angiography strongly correlated with ex vivo measurements of the resected carotid plaque at magnetic resonance imaging (r = 0.979). US angiography depicted unsuspected wall irregularities, ulceration, and dissection.

Aged↗

PubMed2005

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PURPOSE: To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. MATERIALS AND METHODS: All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. RESULTS: EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. CONCLUSION: Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure.

Animals↗

PubMed2005

Pathologic skeletal muscle perfusion in patients with myositis: detection with quantitative contrast-enhanced US--initial results.

PURPOSE: To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. RESULTS: Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. CONCLUSION: Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.

Biopsy↗

PubMed2006

Science to practice: Noninvasive assessment of portal hypertension--can US aid in the prediction of portal pressure and monitoring of therapy?

A method that could be used to accurately assess portal venous pressure would be valuable when diagnosing portal hypertension, evaluating patient prognosis, and monitoring the progress of therapy. Baik et al have suggested that a qualitative noninvasive Doppler US parameter can be used to monitor therapy of portal hypertension. Further clinical investigation is needed to confirm these results and to determine whether hepatic venous Doppler waveform tracings can be used to monitor patient response to therapy. Ongoing research suggests that microbubble contrast agents may enable a more quantitative noninvasive estimate of intravascular pressures with US.

Antihypertensive Agents↗

PubMed2006

Focal liver masses: enhancement patterns on contrast-enhanced images--concordance of US scans with CT scans and MR images.

PURPOSE: To assess prospectively the concordance of enhancement patterns of focal liver masses on contrast material-enhanced ultrasonographic (US) scans with patterns on contrast-enhanced computed tomographic (CT) scans or magnetic resonance (MR) images. MATERIALS AND METHODS: This study was approved by the institutional review board; patients gave informed consent. Contrast-enhanced US and contrast-enhanced CT or MR imaging were performed in 135 patients (62 men, 73 women; mean age, 51 years) with 144 confirmed liver masses. Masses included 49 hepatocellular carcinomas, 13 metastases, 30 hemangiomas, 41 lesions of focal nodular hyperplasia, and 11 others. Randomized image sets from each modality were shown independently to three blinded readers, who answered identical questions about enhancement of the lesion and liver in the arterial and portal venous phases and changes with time. Concordance for modalities was calculated from answers of readers and consensus answers between readers, with 95% confidence intervals (CIs). The kappa values were calculated for interreader agreement. RESULTS: Features of arterial phase enhancement showed concordance of more than 76% for modalities. The highest concordance of 92% (132 of 144), with 95% CI of 86% and 95% (kappa>0.84), was for the presence of peripheral pools and centripetal progression. Concordance in the portal venous phase was lower, with agreement for predominant enhancement of the lesion in 61% (86 of 142), with 95% CI of 52% and 68% (kappa>0.83). Portal venous phase washout occurred in 75% (106 of 142), with 95% CI of 67% and 81% (kappa>0.81). The majority of discordances were for malignancies for which only US depicted no sustained enhancement in the portal venous phase. CONCLUSION: US shows high concordance with CT or MR imaging, especially for the arterial phase. Discordance in the portal venous phase may reflect the tendency of CT and MR contrast agents, unlike microbubbles, to diffuse into interstitium.

Adult↗

PubMed1987

Noncardiogenic pulmonary edema caused by decompression sickness: rapid resolution following hyperbaric therapy.

Noncardiogenic pulmonary edema is a recognized but uncommon manifestation of type 2 decompression sickness. It typically occurs within 6 hours of a dive. Because the adult respiratory distress syndrome in this setting is believed to be due to microbubbles in the pulmonary vasculature, recompression in a hyperbaric chamber has been recommended as a form of therapy. A patient developed noncardiogenic pulmonary edema following a seawater dive to 75 feet. There was complete radiologic and clinical resolution within 5 hours of hyperbaric therapy.

Adult↗

PubMed1991

Benign and malignant nodules in cirrhotic livers: distinction based on blood supply.

The blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities. The portal blood supply was evaluated with computed tomography (CT) during arterial portography (CTAP); the arterial blood supply was evaluated with hepatic angiography, CT angiography, CT following intraarterial injection of iodized oil, or ultrasound following intraarterial injection of carbon dioxide microbubbles. A total of 84 surgically confirmed hepatocellular carcinomas (HCCs) (less than or equal to 3 cm) and 25 areas of adenomatous hyperplasia (AH) were included in the study. At CTAP, a portal blood supply was seen in 96% of cases of AH and only 6% of HCCs (chi 2, P less than .005). In contrast, an arterial supply greater than that of the surrounding liver was verified in 94% of the HCCs and only 4% of the cases of AH (chi 2, P less than .005). The blood supply of areas of AH with atypical hepatocytes and the blood supply of well-differentiated HCCs (Edmondson grade 1) tended to be intermediate between that of AH without atypia and that of HCC that was Edmondson and Steiner grade 2 or greater. Evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early-stage HCC.

Carcinoma, Hepatocellular↗

PubMed1998

Excitotoxin-induced cerebral hyperemia in newborn piglets: regional cerebral blood flow mapping with contrast-enhanced power Doppler US.

PURPOSE: To create regional cerebral blood flow maps with contrast material-enhanced power Doppler ultrasound (US). MATERIALS AND METHODS: In six anesthetized newborn piglets, cerebral hyperemia was induced after intrastriatal injection of 5 mumol of N-methyl-D-aspartic acid. Coronal power Doppler US was performed with a microbubble-based contrast agent, and cerebral blood flow was determined before and at 15, 30, and 60 minutes after injection. Images were digitized and analyzed for changes in mean pixel intensity. A bolus injection curve was constructed by plotting mean pixel intensity versus time, and the area under this normalized curve was compared with cerebral blood flow. RESULTS: Hemispheric cerebral blood flow increased from 40 mL/min/100 g +/- 1 (mean +/- standard error) to 90 +/- 12, 86 +/- 8, and 85 +/- 12 at 15, 30, and 60 minutes after injection, respectively (P < .0001 [analysis of variance]). Hemispheric mean pixel intensity at peak contrast also increased from 69 units +/- 5 to 120 +/- 4, 112 +/- 6, and 98 +/- 13 at 15, 30, and 60 minutes after injection, respectively (P < .003). The area under the normalized curve correlated well with changes in hemispheric and striatal cerebral blood flow (r = .73, P = .0001; r = .62, P = .0001, respectively). CONCLUSION: In the newborn brain, regional blood flow maps can be created accurately with contrast-enhanced power Doppler US.

Animals↗

PubMed1999

Tissue-specific US contrast agent for evaluation of hepatic and splenic parenchyma.

PURPOSE: To evaluate the recently developed ultrasonographic (US) contrast agent SHU 563A, which is specifically taken up by the reticuloendothelial system (RES). MATERIALS AND METHODS: Color Doppler imaging (CDI) was performed in a gel phantom, with SHU 563A microbubbles in stationary suspension. CDI was performed in vivo in five woodchucks with natural hepatomas and in 12 rabbits before and after intravenous bolus injections of SHU 563A (0.16-0.48 mL/kg). After a 15-135-minute delay, the liver and spleen were scanned again, and the image findings were compared with pathologic analysis results. RESULTS: Phantom CDI demonstrated a random mosaic color pattern in spite of the lack of flow. This phenomenon, which is associated with bubble rupture, is termed induced acoustic emission. In vivo, delayed imaging demonstrated acoustic emission signals in normal parenchyma, whereas no mosaic color was seen in regions lacking reticuloendothelial cells (e.g., tumors). Four of 12 VX-2 tumors detected with pathologic analysis were detected with US alone; the remaining eight tumors were detected by using US with contrast agent (100%, P = .0078). Nine of 20 hepatomas were detected at baseline US, whereas 17 were detected after administration of SHU 563A (P = .0215). Acoustic emission enabled detection of hepatic tumors as small as 3 mm in diameter. CONCLUSION: CDI with SHU 563A demonstrates a random mosaic color pattern, even without flow. The characteristic appearance of acoustic emission signals provides a distinctive method of visualizing normal hepatic tissues and substantially improves the detectability of hepatic tumors.

Animals↗

PubMed2000

Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience.

Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.

Adult↗

PubMedDate not supplied

Real-time harmonic contrast material-specific US of focal liver lesions.

Recent advances in contrast material-enhanced ultrasonography (US) mainly include (a) development of low-acoustic-pressure (low-mechanical-index) harmonic software, capable of obtaining real-time images without disrupting contrast material microbubbles, and (b) commercialization of new contrast media ("second-generation" contrast media), capable of producing intense echo signals in this low-mechanical-index setting. With use of low-mechanical-index continuous-mode contrast-enhanced US, the circulatory kinetic models of various focal liver lesions can be displayed dynamically. Hepatic lesions usually have typical perfusion characteristics and enhancement patterns through the various phases of parenchymal enhancement, which helps characterize lesions and, in most cases, allows definitive diagnosis, even among lesions that exhibit very similar baseline appearances. Because of the use of harmonic technologies at low emission frequencies, there is some loss of spatial resolution and overall image quality, typically resulting in a grainy appearance. In addition, lesion depth affects the detectability of vascularity to some degree in that poor signal arises from deep-seated lesions. Moreover, liver attenuation (eg, in patients with steatosis or chronic liver disease) further reduces the sensitivity of contrast-enhanced US. Nevertheless, with its unique capacity to provide images in real time, low-mechanical-index contrast-enhanced US is the dynamic imaging modality of choice in the differential diagnosis of focal liver lesions.

Adult↗

PubMed1997

Changes in myocardial blood volume with graded coronary stenosis.

Vasodilation of microvessels distal to a stenosis results in an increase in myocardial blood volume (MBV). The purpose of this study was to examine the changes in MBV induced by graded coronary artery stenoses by using myocardial contrast echocardiography (MCE). Accordingly, 21 dogs underwent progressive stenosis of a coronary artery in a random order, the severity of which was judged by the pressure distal to it. Total myocardial blood flow (MBF) to the bed distal to the artery (both anterograde and collateral) was measured by injection of radiolabeled microspheres into the left atrium. In seven dogs, anterograde and total MBF were measured at each stenosis stage by injection of different microspheres into the left atrium and directly into the coronary artery, respectively. MBV was calculated by dividing MBF by the mean transit rate of microbubbles injected directly into the coronary artery during MCE. The perfusion bed size of the artery was also measured by MCE. Our major findings are as follows: 1) there is a nonlinear increase in MBV with increasing degrees of coronary stenosis until the coronary stenosis becomes critical; 2) at moderate levels of coronary stenosis, MBV remains constant despite ongoing autoregulation because of reduction in the size of the perfusion bed supplied by the stenotic vessel; and 3) after exhaustion of autoregulation, a decrease in MBV is noted with increasing levels of stenosis. We conclude that assessment of MBV provides insights into myocardial perfusion distal to a coronary stenosis above and beyond that provided by the measurement of MBF alone.

Animals↗

PubMed1999

Echocardiographic determination of risk area size in a murine model of myocardial ischemia.

Genetically altered mice are useful to understand cardiac physiology. Myocardial contrast echocardiography (MCE) assesses myocardial perfusion in humans. We hypothesized it could evaluate murine myocardial perfusion before and after acute coronary ligation. MCE was performed before and after this experimental myocardial infarction (MI) in anesthetized mice by intravenous injection of contrast microbubbles and transthoracic echo imaging. Time-video intensity curves were obtained for the anterior, lateral, and septal myocardial walls. After MI, MCE defects were compared with the area of no perfusion measured by Evans blue staining. In healthy animals, intramyocardial contrast was visualized in all the cardiac walls. The anterior wall had a higher baseline video intensity (53 +/- 17 arbitrary units) than the lateral (34 +/- 13) and septal (27 +/- 13) walls (P < 0.001) and a lower increase in video intensity after contrast injection [50 +/- 17 vs. 60 +/- 24 (lateral) and 65 +/- 29 (septum), P < 0.01]. After MI, left ventricular (LV) dimensions were enlarged, and the shortening fraction was decreased. A perfusion defect was imaged with MCE in every mouse, with a correlation between MCE perfusion defect size (35 +/- 13%) and the nonperfused area by Evans blue (37 +/- 16%, y = 0.77x + 6.1, r = 0.93, P < 0. 001). Transthoracic MCE is feasible in the mouse and can accurately detect coronary occlusions and quantitate nonperfused myocardium.

Animals↗

PubMed1985

Transpulmonary passage of venous air emboli.

Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml X kg-1 X min-1 in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml X kg-1 X min-1. When the air doses were increased to 0.35 ml X kg-1 X min-1, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50% of the animals and reaching 71% for 0.40 ml X kg-1 X min-1. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml X kg-1 X min-1.

Animals↗

PubMed1997

Stabilized bubbles in the body: pressure-radius relationships and the limits to stabilization.

We previously outlined the fundamental principles that govern behavior of stabilized bubbles, such as the microbubbles being put forward as ultrasound contrast agents. Our present goals are to develop the idea that there are limits to the stabilization and to provide a conceptual framework for comparison of bubbles stabilized by different mechanisms. Gases diffuse in or out of stabilized bubbles in a limited and reversible manner in response to changes in the environment, but strong growth influences will cause the bubbles to cross a threshold into uncontrolled growth. Also, bubbles stabilized by mechanical structures will be destroyed if outside influences bring them below a critical small size. The in vivo behavior of different kinds of stabilized bubbles can be compared by using plots of bubble radius as a function of forces that affect diffusion of gases in or out of the bubble. The two ends of the plot are the limits for unstabilized growth and destruction; these and the curve's slope predict the bubble's practical usefulness for ultrasonic imaging or O2 carriage to tissues.

Excipients↗

PubMed2002

Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury.

Although the surface properties of surfactant protein (SP)-B and SP-C are similar, the contributions that either protein may make to lung function have not been identified in vivo. Mutations in SP-B cause lethal respiratory failure at birth; however, SP-B null mice are deficient in both SP-B and SP-C. To identify potential contributions of SP-C to lung function in vivo, the following transgenic mice were generated and exposed to 95% O(2) for 3 days: (SP-B(+/+),SP-C(+/+)), (SP-B(+/+), SP-C(-/-)), (SP-B(+/-),SP-C(+/+)), (SP-B(+/-),SP-C(+/-)), and (SP-B(+/-),SP-C(-/-)). Hyperoxia altered pressure-volume curves in mice that were heterozygous for SP-B, and these values were further decreased in (SP-B(+/-),SP-C(-/-)) mice. Likewise, alveolar interleukin (IL)-6 and IL-1 beta were maximally increased by O(2) exposure of (SP-B(+/-),SP-C(-/-)) mice compared with the other genotypes. Lung hysteresivity was lower in the (SP-B(+/-),SP-C(-/-)) mice. Surfactant isolated from (SP-B(+/+),SP-C(-/-)) and (SP-B(+/-),SP-C(-/-)) mice failed to stabilize the surface tension of microbubbles, showing that SP-C plays a role in stabilization or recruitment of phospholipid films at low bubble radius. Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo.

Animals↗

PubMed2002

Microvascular gas embolization clearance following perfluorocarbon administration.

Effective treatment of vascular gas embolism may be possible with emulsified fluorocarbon compounds. We tested the hypothesis that a fluorocarbon emulsion delivered before gas embolization would enhance bubble motion through the vasculature, favoring more rapid clearance. Air microbubbles were injected into the rat cremaster microcirculation in six groups of rats receiving Perftoran, an emulsified fluorocarbon, or saline immediately before, 2 h before, or after bubble injection. Embolism dimensions and dynamics were observed by using intravital microscopy. Surface area at lodging was equal between groups. Bubbles having smaller volume embolized smaller diameter vessels in the Perftoran pretreatment groups. A higher incidence of bubble dislodgement and larger distal displacement occurred in these two groups, with a 36% decrease in the time to bubble clearance and restoration of blood flow. Intravascular emulsified fluorocarbon administration before gas embolization affected initial bubble conformation, increased bubble dislodgement, and resulted in bubble displacement further into the periphery of the microcirculation. These dynamic events did not occur if embolization preceded fluorocarbon administration.

Algorithms↗

PubMedDate not supplied

Migraine with aura and right-to-left shunt on transcranial Doppler: a case-control study.

Right-to-left shunt (RLS), usually due to patent foramen ovale, is a well-established risk factor for ischemic stroke in young patients, while the role of migraine as an independent factor is still debated. We evaluated 44 patients suffering from migraine with aura, and compared them with 73 patients younger than 50 with focal cerebral ischemia, and 50 controls, asymptomatic for cerebrovascular disease, and without a history of migraine. All the subjects underwent bilateral transcranial Doppler with injection of contrast medium in an antecubital vein. The test was performed during normal ventilation and during Valsalva maneuver, recording both the middle cerebral arteries and the basilar artery. Criteria for diagnosing RLS was the presence of at least 3 microbubbles within 15 s from injection. Eighteen out of 44 migraine patients (41%) showed RLS, as opposed to 8 of 50 controls (16%) (p < 0.005). Twenty-six out of 73 patients with cerebral ischemia had RLS (35%). We conclude that the prevalence of RLS in patients with migraine with aura is significantly higher than in normal controls, and is similar to the prevalence of RLS in young patients with stroke. These findings could be helpful in understanding the relationship between migraine and stroke.

Adolescent↗