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PubMed2004

Precompensated excitation waveforms to suppress harmonic generation in MEMS electrostatic transducers.

Microelectromechanical systems (MEMS) electrostatic-based transducers inherently produce harmonics as the electrostatic force generated in the transmit mode is approximately proportional to the square of the applied voltage signal. This characteristic precludes them from being effectively used for harmonic imaging (either with or without the addition of microbubble-based contrast agents). The harmonic signal that is nonlinearly generated by tissue (or contrast agent) cannot be distinguished from the inherent transmitted harmonic signal. We investigated two precompensation methods to cancel this inherent harmonic generation in electrostatic transducers. A combination of finite element analysis (FEA) and experimental results are presented. The first approach relies on a calculation, or measurement, of the transducer's linear transfer function, which is valid for small signal levels. Using this transfer function and a measurement of the undesired harmonic signal, a predistorted transmit signal was calculated to cancel the harmonic inherently generated by the transducer. Due to the lack of perfect linearity, the approach does hot work completely in a single iteration. However, with subsequent iterations, the problem becomes more linear and converges toward a very satisfactory result (a 18.6 dB harmonic reduction was achieved in FEA simulations and a 20.7 dB reduction was measured in a prototype experiment). The second approach tested involves defining a desired function [including a direct current (DC) offset], then taking the square root of this function to determine the shape of the required input function. A 5.5 dB reduction of transmitted harmonic was obtained in both FEA simulation and experimental prototypes test.

Journal Article↗

PubMed2005

Aberration correction by nonlinear beam mixing: generation of a pseudo point sound source.

Nonlinear beam mixing with microbubbles was explored to create a pseudo point source for aberration correction of therapeutic ultrasound. A damping coefficient for a bubble driven by a dual frequency sound field was derived by revisiting Prosperetti's linearized damping model. As a result, the overall damping term for dual frequency was obtained by linear summation of two damping terms for each frequency. The numerical simulation based on the bubble model suggests that the most efficient size range to generate a 1 MHz frequency from 4 MHz and 5 MHz sound sources is 2.6 to 3.0 microm. Furthermore, this size range constitutes the primary distribution of a specific ultrasound contrast agent. When a chamber of 0.1% of the diluted agent is sonified by 4 MHz and 5 MHz sound beams with 80 degrees incident angle between them, an approximately 100 Pa, 1 MHz difference frequency signal can be measured approximately 10 cm away. In addition, the received 1 MHz difference frequency signal shows omni-directional characteristics, even though the overlap zone of the two sound beams is on the order of the difference frequency wavelength. Therefore, the induced sound source can be considered as a pseudo point source and is expected to be useful for aberration correction for therapeutic ultrasound.

Animals↗

PubMed2004

Hepatopulmonary syndrome: a concern for the anesthetist? Pre-operative evaluation of hypoxemic patients with liver disease.

Liver cirrhosis and other chronic hepatic diseases are followed in a subset of affected patients by gas exchange abnormalities resulting from a syndrome called hepatopulmonary syndrome (HPS). The structural basis of this clinical entity is an alteration of pulmonary vasculature resulting in abnormal vasodilatation and mismatching of ventilation and perfusion of the lung. Dilatation of the capillary bed near the gas exchange area is the most important factor implicated; it precludes O2 molecules diffusing to the centrum of the dilated vessels to oxygenate venous blood. Contrast (microbubbles) echocardiography and lung perfusion scan are, respectively, the screening tests with the highest sensitivity and specificity for HPS diagnosis. Because of the high morbidity and mortality of HPS, clinicians have been trying to understand the pathophysiology of pulmonary vasodilatation in the hope that the process can be reversed pharmacologically or surgically. An imbalance between production and clearance of vasoactive circulating substances has been implicated in the pathogenesis of HPS with glucagon and nitric oxide among the principal responsible factors. To date various molecules have been implicated for therapy but without definitive positive results. Liver transplantation remains the only real therapy for HPS, and resolution of gas exchange defects outlines the possible functional reversible nature of vascular abnormalities of this syndrome. The need to perform surgery under general anesthesia for hepatic and extrahepatic procedures in patients with HPS is followed by an increased peri-operative risk. The authors emphasize the role of pre-operative clinical evaluation for proper patient management during the peri-operative period.

Anesthesia↗

PubMed2005

Histological characterization of microlesions induced by myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography (MCE) has been shown to have a potential for apparently reversible side effects related to the interaction of ultrasound with the contrast microbubbles, including premature ventricular contractions and microvascular leakage. We investigated the potential for high-dose MCE to induce histologically definable microlesions. METHODS: Myocardial contrast echocardiography with 1:4 end-systolic triggering was performed at 1.5 MHz and 1.7 mechanical index in a short axis view of the left ventricle in rats. Two high doses (500 microl/kg) of Optison agent were given 5 minutes apart during 10 minutes of echocardiography. For histology, the hearts were perfused and fixed in 10% neutral-buffered formalin. Slides from rats sacrificed 1 day after MCE were scored blind by a pathologist, and, in addition, photomicrographs in the anterior half were evaluated by digital image analysis. RESULTS: In rats sacrificed 10 minutes after MCE, microvascular leakage and petechiae were highly significant. However, lesions displaying necrotic debris associated with inflammatory infiltrates were not histologically evident at this time. Heart samples 24 hours after MCE showed microlesions with inflammatory infiltrates scattered primarily over the anterior half of the sections. Pathologically, there was inflammatory cell infiltration in areas of 0.6 +/- 0.5% for shams and 3.6 +/- 3.6% for MCE (P < 0.01). Analysis of photographs from the anterior wall found microlesion areas of 0.5 +/- 0.8% for shams and 7.4 +/- 5.0% for MCE (P < 0.02). For rats sacrificed 1 week and 6 weeks after MCE, the microlesions healed to form small fibrous regions interspersed with normal myocytes. CONCLUSION: High-dose MCE has a potential for causing microscale lesions in the myocardium and the possibility of therapeutic applications.

Albumins↗

PubMed1994

New interpretation and management of dry lung syndrome: a case report.

A premature female infant with life-threatening respiratory distress which was diagnosed as 'dry lung syndrome' is reported. The mother had 4 weeks of large volume leakage of the amniotic fluid due to premature rupture of the fetal membranes (PROM) at 23 weeks' gestation. The infant was born after 27 weeks' gestation (birthweight, 1016 g) and was suffering severe respiratory distress. Although a chest radiogram and gastric juice microbubble test did not improve the possibility of respiratory distress syndrome (RDS), very high ventilator settings did not improve her respiratory disorders. Considering the infant's deteriorating respiratory status and the prolonged leakage of the amniotic fluid, we suspected the presence of pulmonary hypoplasia. Although an attempt at high frequency oscillation (HFO) to rescue this infant had no effect, intratracheal instillation of epinephrine (EP) showed dramatic improvement of her respiratory status. This clinical course showed that the patient did not have pulmonary hypoplasia but might have severe airway obstruction and this airway obstruction may be the major cause of 'dry lung syndrome'. We postulate that when a newborn with suspected pulmonary hypoplasia is unresponsive to respiratory support. HFO should be administered. If HFO is ineffective in relieving the respiratory distress, one should suspect the presence of airway collapse and administer a bronchodilator such as EP. If the infant improves, a diagnosis of 'dry lung syndrome' may be assumed.

Adult↗

PubMed2004

Ovarian cancer detected non-invasively by contrast-enhanced power Doppler ultrasound.

Overall, about one-third of women operated upon because of suspected ovarian cancer turn out to have benign disease. This proportion will be even higher when the tumours are small. A more accurate method of determining which are malignant would reduce the number of unnecessary referrals to the cancer centre and increase the scope for conservative management. This pilot study of ultrasound and intravenous microbubble contrast in 20 women with small ovarian tumours enabled the identification of all four malignant lesions with good inter-observer agreement. These preliminary findings suggest that intravenous contrast improves the ultrasound identification of small ovarian malignancies and may provide an accurate way of selecting women who require to be referred urgently for surgery under the auspices of a gynaecological oncologist. The remainder might be considered for laparoscopic surgery or even for observation in some cases.

Adult↗

PubMed2006

Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.

AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients. PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study. CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.

Adult↗

PubMed1991

Comparison of a steady flow pump to a preload responsive pulsatile pump in left atrial-to-aorta bypass in canines.

A unique preload responsive pulsatile pump was compared to a centrifugal pump in total cardiac support in 25-kg canines (n = 6, each group) in the left atrial-to-aorta mode during 5 h of ventricular fibrillation. With steady flow, there was immediate drop in output from 2.1 +/- 1.0 L/min to 1.4 +/- 0.3 L/min, followed by further reduction to 0.9 +/- 0.2 L/min during 5 h of ventricular fibrillation. With a pulsatile pump, there was no significant reduction from control of 2.4 +/- 0.6 L/min and no decline during 5 h of ventricular fibrillation. With steady flow, systemic vascular resistance (SVR) rose significantly from 1,762 dyne-s-cm-5 immediately on pump to 3,013 dyne-s-cm-5 at 5 h. With physiologic pulsatile flow, significant elevation of SVR did not occur. When stressed, due to diminished left atrial return, the centrifugal pump displayed line chatter and streaks of microbubbles, whereas the pulsatile pump did not. Crystalloid volume replacement with the centrifugal pump was 6.5 +/- 1.9 L, and with the preload responsive pulsatile pump, 5.6 +/- 1.3 L. It is concluded that in the left atrial-to-aorta mode during 5 h of ventricular fibrillation and with comparable volume replacement, total cardiac support of canines is associated with lower SVR with physiologic pulsatile flow and is not accompanied by line chatter and cavitation with this preload responsive pump.

Animals↗

PubMed1990

Echocardiographic contrast in two-dimensional echocardiography: new applications for an old technique?

Although Gramiak and Shah first introduced the technique of using contrast enhanced two-dimensional echocardiography in 1968, it has seen a resurgence of new and varied applications. Three of the areas of interest are in the use of microbubble enhanced contrast agents to evaluate: (1) regional myocardial blood flow; (2) regional myocardial function; and (3) myocardial ischemic areas and infarct size. Whether these new approaches will have applications and value in the clinical laboratory is still a matter of conjecture. The objective of this review is to briefly summarize the potential uses and the advantages and disadvantages of each application.

Animals↗

PubMed1991

Echo contrast agents improve flow display of color Doppler: in vitro studies.

Flow detection by color Doppler is impaired by low velocity of flow and increasing attenuation and depth of ultrasound penetration. The effects of increased echogenicity on flow detection (Toshiba SSH 65A) were thus studied in a flow model, which yielded similar strengths of Doppler signals as seen in the clinical routine, by adding microbubble solutions to the blood analog fluid (45% aqueous glycerin) and comparing signal strength (score 0-5) prior to and after contrast. The flow within the plexiglass tube with less than 3 degrees angle of coincidence for Doppler interrogation was laminar with a parabolic velocity profile at physiological velocities and pressures. In comparison with various contrast agents at a flow velocity of 18 cm/sec and 19 dB attenuation, flow was not detectable in control color Doppler, after 4 mL of the blood analog fluid, and after 4 mL of an agitated saline solution 9 mg/mL, but visible after 4 mL of Echovist, a polysaccharide solution with reproducible bubble size and concentration and after 4 mL of an agitated polygelatin solution. Increasing concentration of Echovist (50-400 mg/mL) improved flow detection. Echovist 200 mg/mL enhanced the score by 1.1 + -0.6 for velocities 5-20 cm/sec (P less than 0.01), by 1.6 + -0.8 for 40-100 cm/sec (P less than 0.001), and by 1.1 + -0.6 for velocities greater than 150 cm/sec (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMed1994

Quantification of images obtained during myocardial contrast echocardiography.

This article describes currently used quantitative methods for analysis of data obtained during myocardial contrast echocardiography. The specific issues addressed are: obtaining time-intensity curves from the myocardium in order to derive transit rates of microbubbles through the myocardium; defining spatial distribution of flow within a myocardial segment; and color-coding algorithms used to define the extent and magnitude of hypoperfusion within a cross-section of the heart. These methods are being adopted by several companies dealing with acquisition and analysis of echocardiographic data and should become available soon for clinical use.

Algorithms↗

PubMed1997

Identification of Perfusion Abnormalities Using FSO69, a Novel Contrast Agent, in Conscious Dogs.

Recent advances in the production of echocardiographic contrast agents has resulted in the ability to delineate areas of hypoperfusion after coronary occlusions and stenoses following their intravenous injection. Most of these studies though have been done in open chest animals. This study was done to determine if we could assess myocardial perfusion following the intravenous administration of FSO69, a suspension of perfluoropropane filled albumin microspheres (3.6 µm average microbubble size, concentration 8 x 10(8)), in spontaneously breathing closed chest dogs. Twenty-seven mongrel dogs were instrumented on day 1. The chest was then closed and the dogs were restudied 3-7 days later, while spontaneously breathing. Homogeneous perfusion was observed in most dogs by all three independent and blinded observers. Perfusion abnormalities were likewise identified in most instances by all blinded reviewers on interventions designed to decrease regional blood flow. A good correlation between perfusion defect size between investigators was observed. In summary, our data suggest that FSO69 can be used to assess regional myocardial perfusion in spontaneously breathing dogs. These results support its use in humans.

Journal Article↗

PubMed1997

Biological Effects of Ultrasound. The Perceived Safety of Diagnostic Ultrasound Within the Context of Ultrasound Biophysics: A Personal Perspective.

This brief review addresses the issue of health and safety from exposure to diagnostic ultrasound. The exemplary historical record of diagnostic ultrasound exposures is coupled with great patient benefit. However, the power outputs of clinical devices have been increasing over the past decade such that inertial cavitation seems reasonably likely to occur if appropriate gas nuclei are present. The use of microbubble contrast agents for certain diagnostic procedures ensures a well nucleated system. Under such conditions, the use of low signal output levels and short exam times will decrease the chance of cavitation related bioeffects.

Journal Article↗

PubMed1997

Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results.

BACKGROUND: In fundamental and second harmonic echocardiography new contrast media opacify the cavities and reduce the difference in the gray level between the cavity and the myocardium thus obscuring the borders of the myocardium. OBJECTIVES: The aim of the study was to examine the potential usefulness of second harmonic power Doppler imaging (HPD) in providing adequate delineation of the myocardium from the left ventricular (LV) and right ventricular (RV) cavities during intravenous contrast echocardiography. Using HPD, microbubbles in a cavity or a tissue are imaged as colored pixels superimposed on a conventional B-scan image. METHODS: In a pilot study, three healthy volunteers and two patients with ischemic heart disease were investigated using an ATL-HDI 3000 echo system. Four chamber views were obtained using fundamental B-scan, harmonic B-scan two-dimensional echocardiography (H2D) and HPD following intravenous injections of 3 g Levovist(R). RESULTS: Using intermittent scanning/recording, H2D and HPD provided intensive and homogenous contrast effects in the RV and LV cavities. Good delineation of the myocardium was found in all subjects using HPD, whereas in two of three volunteers and in one of two patients ventricular septal and apical endocardial borders were obscured during H2D. No obvious change in myocardial backscatter was visually found with H2D. However, in all three healthy volunteers and in one of two patients, HPD recordings demonstrated patchy and reticular patterns in the myocardium, which were different from the homogenous signals in the LV cavity. These are consistent with imaging of intramyocardial coronary vessels. CONCLUSIONS: HPD with intravenous Levovist is feasible. This technique demonstrated good delineation of ventricular cavities from the myocardium as well as presence of visible contrast in the myocardium. This pilot study justifies further clinical trials to evaluate the clinical benefit of this approach.

Journal Article↗

PubMed1999

Contrast-Enhanced Doppler Ultrasound of Renal Artery Stenosis: Prologue to a Promising Future.

Over the past few years, there has been extensive research for a reliable, noninvasive, and nonionizing imaging method to screen for renal artery stenosis (RAS). Doppler ultrasound (US) is one of many modalities that have been evaluated for the detection of RAS. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories, however, have prevented universal acceptance of this technique as a reliable screening test for RAS. Recently, the introduction of US contrast agents has substantially expanded the potentials of color Doppler US. The use of microbubble echo enhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. In addition, contrast-enhanced harmonic Doppler US can currently provide objective functional assessment of RAS through analysis of time-intensity renal enhancement curve. State-of-the-art contrast-enhanced Doppler US seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension and a tool for follow-up of patients who undergo revascularization procedures.

Journal Article↗

PubMed1999

Rapid Three-Dimensional Myocardial Contrast Echocardiography: Volumetric Quantitation of Nonperfused Myocardium After Intravenous Contrast Administration.

Current acquisition methods for quantitative three-dimensional myocardial contrast echocardiography require long acquisition times and therefore require the invasive administration of deposit contrast agents administered intra-arterially or into the left atrium. This study addressed the feasibility of obtaining accurate and precise quantitative volumetric measurements of nonperfused myocardium after an intravenous bolus of echocardiographic contrast agent using a rapid three-dimensional myocardial contrast echocardiographic acquisition technique. An open-chest pig model of acute left anterior descending coronary artery (LAD) occlusion was used. After LAD ligature, an intravenous bolus of contrast agent was given and images were obtained over a 12-second period using a continuously rotating transducer placed at the apical position. There was no significant microbubble destruction during the rotational acquisition period as measured by differences in mean gray scale values of apical, mid, and basal myocardial regions between the first and last image frames of acquisition. Calculated volumes of nonperfused myocardium demonstrated significant agreement and correlation (mean difference +/- SD = -0.30 +/- 1.71 cm(3); r = 0.89; P < 0.01; y = 1.06x - 1.08) with anatomic specimens. When expressed as percent of total LV volume being nonperfused, the mean difference +/- SD was 2.1 +/- 3.6%, r = 0.94, P < 0.01, and y = 1.33x - 4.08. We conclude that accurate and precise measurements of nonperfused myocardium after an acute LAD coronary artery occlusion can be obtained after the intravenous bolus administration of a contrast material when a rapid 12-second acquisition with a continuously rotating transducer is used.

Journal Article↗

PubMed2000

Measurement of left ventricular volumes and ejection fraction after intravenous contrast agent administration using standard echocardiographic equipment.

The enhancement of endocardial border delineation using second harmonic imaging and contrast administration improves the measurement of ventricular volumes. In the majority of existing echocardiographic equipment, however, harmonic imaging is not yet available. The aim of this study was to assess the feasibility of the measurement of left ventricular volumes and ejection fraction after intravenous administration of the contrast agent Levovist using standard echocardiographic equipment and fundamental imaging modality. In 10 patients with good-quality two-dimensional echo imaging, 4 g (400 mg/mL concentration) of Levovist was injected intravenously. Hewlett-Packard Sonos 2000 ultrasound equipment without second harmonic imaging capability was used. To avoid the destruction of microbubbles, the echo machine was set to produce only one end-systolic and one end-diastolic frame in each cardiac cycle (dual triggering). Native and contrast imaging measurements of left ventricular volumes and ejection fractions calculated by modified Simpson's rule were compared in the fundamental mode. Intraobserver and interobserver variability values were assessed. End-diastolic volumes in native continuous and triggered mode and by contrast echo were 126 +/- 48, 121 +/- 46, and 130 +/- 50 mL, respectively (NS), whereas end-systolic volumes were 79 +/- 48, 76 +/- 45, and 79 +/- 46 mL, respectively (NS). Calculated ejection fraction using the three different imaging modalities were 0.41 +/- 0.16, 0.41 +/- 0.16, and 0.42 +/- 0.16 (NS). The intraobserver and interobserver reproducibility values were excellent in triggered mode. Standard echocardiographic equipment with fundamental imaging modality in the triggered mode is suitable for the measurement of left ventricular volumes after intravenous Levovist administration. In clinically difficult patients, contrast echocardiography in triggered mode may be applied even if echocardiographic equipment does not have harmonic imaging possibility.

Cardiomyopathy, Dilated↗

PubMed2000

Design of an ultrasound contrast agent for myocardial perfusion.

Myocardial contrast echography (MCE) has been a major research objective in cardiovascular ultrasound for almost two decades. The design of a contrast agent fulfilling the needs of MCE requires taking into consideration a number of points: a basic decision has to be made whether a deposit agent or a free-flowing agent would be more appropriate and whether an agent active at low/medium mechanical index (MI) is preferable to an agent active only at high MI; only a small percentage of the cardiac output enters the coronary microcirculation, which means that highly sensitive bubble detection methods, such as harmonic imaging or pulse inversion, are needed; the low velocity of blood in the microcirculation that leads to extensive bubble destruction during imaging means that intermittent imaging and/or an agent active at low MI is (are) required; the duration of the contrast effect must be sufficient to allow a complete examination and is affected by the rate of contrast administration; the performance of the contrast agent should not be equipment-dependent. The ultimate goal in MCE is to be able to quantify blood flow in the various segments to determine if adequate oxygenation is achieved. Ultrasound-mediated bubble destruction followed by the measurement of bubble replenishment kinetics opens new perspectives for quantification. SonoVue is a free-flowing ultrasound contrast agent made of sulphur hexafluoride microbubbles stabilized by a highly elastic phospholipid monolayer. SonoVue is able to produce myocardial opacification at a wide range of acoustic pressures and in particular at MIs as low as 0.1. Its performance is not equipment-dependent. Good results for myocardial opacification have been observed in all animal species tested (dogs, minipigs, rabbits), using continuous as well as intermittent imaging. Trials are in progress to demonstrate the clinical utility of SonoVue for rest and stress perfusion studies, in particular for the diagnosis of CAD, the detection of myocardial infarction, the assessment of the success of interventions and myocardial viability, and the detection of hibernating myocardium.

Animals↗