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PubMed1999

Spontaneous gas bubbling in microporous oxygenators.

During operation of the microporous membrane oxygenators at some conditions, gas microbubbles penetrate into the blood. This effect, so-called spontaneous bubbling, takes place even when the blood pressure is higher than the gas pressure. This phenomenon was confirmed experimentally both in a model cell with hydrophobic microporous hollow fibers being used in the oxygenators and in in vitro tests on the actual microporous hollow fiber oxygenator. We proposed a mechanism of spontaneous gas bubbling into liquid that contains dissolved gases. Because of a partial pressure gradient, the dissolved gases and water vapors are transported from blood into the gas pore. This causes Stefans gas flow directed from the liquid-gas interface. Because of the high hydraulic resistance of the micropores, gas pressure at the meniscus increases up to gas bubbling. A mishandled priming of the oxygenator as well as the blood pressure pulsation caused by the roller pump operation contribute to spontaneous gas bubbling in the microporous oxygenators. The flow and pressure in the hydrophobic pores were calculated for various gases.

Algorithms↗

PubMed2004

Localizing and quantifying ablation lesions in the left ventricle by myocardial contrast echocardiography.

INTRODUCTION: The inability to determine the extent and intramural depth of ablation lesions can hamper the success of catheter ablation. The study tested the feasibility of differentiating radiofrequency ablation lesions from normal myocardium and quantifying their dimensions by myocardial contrast echocardiography (MCE). METHODS AND RESULTS: In 11 normal dogs, we created 14 focal and 4 linear lesions at different left ventricular sites. MCE was performed both before and after ablation by using an intracardiac echocardiography catheter (9 MHz) and infusing contrast microbubbles through the left coronary artery. We initially used two-dimensional MCE to image focal lesions and subsequently three-dimensional MCE to image linear lesions. An independent observer examined the lesion pathology. We found that intracardiac echocardiography alone could not delineate lesion dimensions. However, after ablation, MCE localized the lesions as well-defined, low-contrast areas within the normally opacified myocardium. Lesion dimensions by MCE immediately after ablation and 30 minutes later were similar. In 12 focal lesions, the average maximum depth (5.55 +/- 1.38 mm) and average maximum diameter (10.38 +/- 2.09 mm) by MCE were in excellent agreement with the pathologic depth (5.20 +/- 1.45 mm) and diameter (10.61 +/- 1.67 mm). Two focal lesions could not be detected by MCE and later were found to be superficial. Three-dimensional MCE correctly reconstructed the extent and shape of linear lesions compared to pathology (length: 18.7 +/- 5.7 vs 18.5 +/- 5.6 mm; maximum longitudinal cross-sectional area: 81.2 +/- 9.6 vs 76.0 +/- 10.3 mm2). CONCLUSION: MCE accurately localized and quantified radiofrequency ablation lesions in the normal left ventricle. This new application of MCE may advance ablation for managing ventricular arrhythmias that involve intramural or epicardial regions by providing instantaneous anatomic feedback on the effects of ablation during catheterization.

Animals↗

PubMed2001

Blood flow assessment by ultrasound-induced destruction of echocontrast agents using harmonic power Doppler imaging: which parameters determine contrast replenishment curves?

OBJECTIVE: To evaluate the feasibility of flow determinations by contrast replenishment using harmonic power Doppler imaging (H-PDI). BACKGROUND: The application of indicator dilution principles on contrast echocardiography is limited by numerous methodical problems. Recently, a new method was introduced that relies on ultrasound-mediated microbubble destruction and evaluation of the contrast replenishment. METHODS: Definity, a perfluorocarbon-derived contrast agent under development, was continuously infused into a steady flow phantom and H-PDI registrations were performed within a silicone tube (d = 8 mm). Replenishment interval between destruction and imaging frame was varied from 0.04-2 seconds. Nonlinear curve fitting was performed using an exponential mathematical model. RESULTS: Strong linear correlation between contrast dose and maximum signal intensity as well as between flow and the slope variable beta of the replenishment curve was found for all settings (r > 0.96). Maximum signal intensity and contrast replenishment rate were found to be a function of emission power and were significantly influenced by depth and focus position. CONCLUSION: The feasibility of flow assessment using replenishment curves obtained by H-PDI was demonstrated. However, in experimental conditions, flow analysis was severely influenced by ultrasound system settings and imaging conditions such as emission power, sound field geometry, and investigation depth. For a clinical use of this promising approach, algorithms that take specific system settings and imaging conditions into account have to be found. Imaging modalities that enable a most homogeneous scan field are best suited for the assessment of contrast replenishment.

Contrast Media↗

PubMed2001

Myocardial contrast echocardiography: a new gold standard for perfusion imaging?

Recent developments have permitted myocardial contrast echocardiography (MCE) to become a new method of noninvasively assessing myocardial perfusion in humans. Preliminary studies of myocardial perfusion imaging during adenosine, dipyridamole, and dobutamine stress echocardiography have shown excellent agreement with either radionuclide uptake or quantitative angiography. This article reviews the recent advances in microbubble technology, ultrasound imaging, and myocardial physiology that have made contrast echocardiography a potential new gold standard for perfusion imaging in the new millennium.

Coronary Circulation↗

PubMed2001

Power Doppler myocardial contrast echocardiography using an improved multiple frame triggered Harmonic Angio technique.

Although B-mode harmonic, intermittent-triggered myocardial contrast echocardiography (MCE) is a well-established technique, a variety of MCE techniques have been introduced recently to improve myocardial opacification. One such technique uses a power Doppler method in conjunction with multiple frame triggering (MFT), but has been limited by nonuniform microbubble destruction and blooming as well as motion artifacts. Utilizing two different contrast agents, Definity and Optison, we tested the feasibility of an improved version of Harmonic Angio MFT that utilizes a lower transmit frequency, reduced packet size, and more stringent wall filter in normal volunteers and in patients with known perfusion defects. The results showed that Harmonic Angio MFT produced fill frames with readily visible opacification and destruction frames with little visible opacification. The patterns of opacification also correlated with the expected perfusion patterns in both groups of subjects. Thus, Harmonic Angio MFT appears to be a promising new MCE technique.

Adult↗

PubMed2001

Ultrasound-enhanced thrombolysis.

Problems with current thrombolytic therapy include slow and incomplete thrombolysis and frequent bleeding complications. Increasing evidence from in vitro, animal, and initial patient studies indicates that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness and decrease bleeding complications. Numerous studies in vitro demonstrate that low intensity ultrasound increases enzymatic fibrinolysis through mechanisms that include improving drug transport, reversibly altering fibrin structure, and increasing tPA binding to fibrin. These observations have been confirmed in animal models that demonstrated that ultrasound delivered transcutaneously or with an endovascular catheter accelerates thrombolysis in models of venous, arterial, and small vessel thrombosis. Ultrasound delivered at higher intensities using either an endovascular vibrating wire or transcutaneously in conjunction with stabilized microbubbles can cause mechanical fragmentation of thrombus without administration of plasminogen activator. Recent studies indicate that ultrasound at lower frequencies in the range of 20-40 kHz has a greater effect on thrombolysis with improved tissue penetration and less heating. These studies form the basis for clinical trials investigating the potential of ultrasound as an adjunct to improve thrombolytic therapy.

Animals↗

PubMed2001

Augmentation of ultrasound-induced clot disruption by nongas-filled microparticles.

The augmentation of ultrasound-induced clot disruption by echocardiographic contrast microbubbles may be a direct mechanical erosive effect of the clot by the microparticles. To further assess this hypothesis, we evaluated the rate and extent of clot disruption by using external ultrasound and nongas-filled microparticles (HAEMACCEL and HAES). Human blood clots were used in this in vitro study. The percent clot reduction using the combination of ultrasound and microparticles was dose dependent and significantly higher than that with microparticles alone.

Animals↗

PubMed2001

The use of ultrasound for drug delivery.

Ultrasound has been in use for the last three decades as a modality for diagnostic imaging in medicine. Recent studies have shown that nonthermal ultrasound energy could be applied for targeting or controlling drug release. This new concept of therapeutic ultrasound combined with drugs has induced interest in various medical fields. Enhanced effects of thrombolytic agents such as urokinase and TPA with acoustic energy have been demonstrated. Ultrasound transducer-tipped catheters are being developed for treatment of cardiovascular diseases. Other devices with ultrasound transducers implanted in transdermal drug patches are also being evaluated for possible delivery of insulin through the skin. Echo contrast microbubbles could also be used to carry and release genes to various tissues and lesions. Chemical activation of drugs by ultrasound energy for treatment of cancers is another new field recently termed "sonodynamic therapy." Various examples of ultrasound application are under investigation that could lead to revolutionary drug delivery systems of the future.

Drug Delivery Systems↗

PubMed2001

Power Doppler dual-frame triggering of myocardial contrast echocardiography: a quantitative video intensity analysis.

AIM: The purpose of this study was to define the pattern of myocardial contrast observed during triggered dual-frame power Doppler imaging. METHODS AND RESULTS: Ten patients with no previous history of myocardial infarction underwent a continuous intravenous infusion of Optison at 0.5 ml/min. Triggered, sequential dual-frame power Doppler imaging was performed from an apical four-chamber view using a prototype Acuson Sequoia imaging system. The average triggering interval was once every four cardiac cycles, and the average interval between sequential frames was 50 msec. Video intensity analysis was performed in five myocardial regions of interest, and the percent decrease in video intensity of the destruction frames in each region of interest was determined by subtracting the destruction frame video intensity from the fill frame video intensity. The percent decrease in video intensity varied significantly by myocardial location (P < 0.001), with greater destruction seen in the apical than in the basal regions. CONCLUSION: This preliminary study demonstrates that power Doppler dual-frame triggering produces nonuniform decreases in video intensity, which likely represent nonuniform microbubble destruction. These results have important implications for the interpretation of myocardial perfusion patterns using this technique.

Contrast Media↗

PubMed2002

Multicenter evaluation of SonoVue for improved endocardial border delineation.

OBJECTIVES: Two multicenter studies were conducted to evaluate the safety and efficacy of SonoVue as a contrast agent for enhanced left ventricular endocardial border delineation (LVEBD), and to compare the efficacy of SonoVue and Albunex in adult patients with a suboptimal, nonenhanced echocardiogram. BACKGROUND: The use of contrast to enhance echocardiographic assessment of LVEBD is well-established. SonoVue is a new microbubble contrast agent that contains sulfur hexafluoride. METHODS: Patients were randomized to receive four injections of SonoVue (0.5, 1, 2, and 4 ml), or two injections of Albunex and two injections of hand-agitated saline (0.08 and 0.22 ml/kg). Echocardiographic images were evaluated at the study centers and by four blinded, offsite reviewers for degree of left ventricle opacification (LVO), duration of contrast enhancement, and LVEBD. RESULTS: LVO scores were significantly higher for all doses of SonoVue. Patients with complete LVO ranged from 34%-87% for SonoVue and from 0%-16% for Albunex. The mean duration of useful contrast effect ranged from 0.8-4.1 minutes for SonoVue and < 15 seconds for Albunex. Mean increases in LVEBD scores ranged from 3.8-18.2 for SonoVue and 0.1-4.3 for Albunex. SonoVue (cumulative 7.5 ml dose) was well-tolerated, with a safety profile similar to that observed in the control group. CONCLUSIONS: SonoVue is superior to Albunex for improving visualization of endocardial borders in patients with suboptimal noncontrast echocardiograms. Optimal increases in LVEBD, LVO, and duration of useful contrast effect were observed at the 2.0 ml dose of SonoVue.

Adult↗

PubMed2002

Endocardial border delineation during dobutamine infusion using contrast echocardiography.

BACKGROUND: A significant percentage of pharmacologic stress echocardiograms produce suboptimal images despite the use of second harmonic imaging. Intravenous continuous infusion of myocardial ultrasound contrast may enhance endocardial border delineation during dobutamine-atropine stress echocardiography (DASE), improving wall-motion analysis. PATIENTS AND METHODS: We prospectively studied 68 patients (41 males and 27 females), mean age 58 years, with DASE during intravenous infusion of contrast using second harmonic imaging. Dobutamine was infused in scalar doses of 5 microg/kg/min to 40 microg/kg/min, and atropine was administered in doses of up to 1 mg. We diluted 0.1 mL of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles into 80 mL of saline solution, which was used for continuous intravenous infusion. Blinded reviewers used a 16-segment model at rest and peak DASE to analyze segmental wall delineation in two sets of images for each patient, with and without contrast. An endocardial delineation score of 0-3 (nondelineated to excellent delineation) was given to each segment. An endocardial delineation score index (EDSI), the number of endocardial delineation scores for each set of images divided by 16, was created. RESULTS: The analysis of the mean EDSI for the 2176 segments was 1.46 (+/- 0.43) at rest and 1.30 (+/- 0.48) at peak for noncontrast images and 2.22 (+/- 0.52) and 2.29 (+/- 0.52) for contrast images. Complete left ventricle opacification was obtained in all patients, with a mean dose of 4 mL/min, although in 15 (22%) patients, signs of apical bubble destruction occurred. There were 1768 (81%) of 2176 segments delineated without contrast enhancement and 2057 (95%) of 2176 with enhancement (P < 0.05). CONCLUSION: Continuous infusion of myocardial ultrasound contrast improves endocardial border delineation using second harmonic imaging in patients undergoing DASE.

Adult↗

PubMed2002

Clinical experience in the detection of coronary artery disease with myocardial contrast echocardiography.

Myocardial contrast enhancement following intravenous infusions or injections of perfluorocarbon-containing microbubbles has now been observed consistently in humans. Currently, the major challenge facing us is interpreting accurately what we see. The myocardial contrast patterns we observe have, thus far, been shown to detect myocardial perfusion abnormalities during dipyridamole, adenosine, and dobutamine stress echocardiography. They also have been shown to detect zones of no reflow following coronary revascularization in patients with acute myocardial infarction. These preliminary data will require validation in larger multicenter clinical studies.

Animals↗

PubMed2002

Assessment of myocardial viability with myocardial contrast echocardiography.

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.

Acute Disease↗

PubMed1999

Clinical and imaging features of testicular torsion: role of ultrasound.

The early and accurate diagnosis of testicular torsion remains a clinical challenge. The implications of a missed diagnosis have emphasized the need for a non-invasive test for confirming testicular ischaemia; a problem highlighted by difficulties in establishing the diagnosis clinically. Understandably, the advent of colour Doppler ultrasound (CDUS) (and subsequently 'power' Doppler and microbubble ultrasound contrast), has been greeted with enthusiasm. However, as in other fields of medicine, a policy placing sole reliance on a single technique is likely to be flawed. This review will critically evaluate the role of CDUS and other imaging modalities in the diagnosis of testicular torsion.

Age Factors↗

PubMed1999

Mobile echoes on prosthetic valves are not reproducible. Results and clinical implications of a multicentre study.

AIMS: To test the hypothesis that inter-observer variability accounts for the wide variation in reported prevalences of fibrin strands on prosthetic heart valves and to develop criteria for their identification and reporting. METHODS AND RESULTS: A videotape with 30 sequences of prosthetic heart valves imaged by transoesophageal echocardiography and showing abnormalities such as strands, microbubbles, and spontaneous echocardiographic contrast, was assessed in 13 European and three American centres. There were three duplicated examples, unbeknown to the observers. Definitions and reported prevalence rates of the abnormalities were analysed, and inter- and intra-observer agreement estimated with the kappa statistic. Mobile echoes were identified in 40 to 80% of the sequences on the tape. The reported prevalence of mobile echoes correlated with the time spent reporting the tape. There was moderate inter-observer agreement for the identification of any mobile echoes (kappa = 0.38), but no agreement for their labelling (kappa = 0.22), in spite of similar definitions. Intra-observer reproducibility was good (agreement in 76% of the reduplicated sequences). CONCLUSIONS: The true prevalence and potential significance of mobile echoes on prosthetic heart valves cannot be assessed unless inter-observer consensus on echocardiographic criteria for identifying such echoes is reached.

Adult↗

PubMed2002

Real time contrast echocardiography--a new bedside technique to predict contractile reserve early after acute myocardial infarction.

AIMS: Power pulse inversion echocardiography is a new technique by which contrast microbubbles can be visualised in real time within the myocardium, enabling simultaneous assessment of myocardial function and microvascular integrity, which is a prerequisite for myocardial viability. We aimed to determine whether microvascular integrity using power pulse inversion can be used to predict contractile reserve early after myocardial infarction. METHODS AND RESULTS: We studied 19 stable patients 5.1(1.6) days after presentation using low dose dobutamine stress echocardiography and power pulse inversion using slow bolus intravenous injections of Optison. A 16-segment left ventricular model was used to define wall thickening at baseline and following low dose dobutamine infusion (1, normal; 2, reduced; 3, absent), and contrast opacification (1, homogeneous; 2, heterogenous or reduced; 3, absent). The techniques were compared on a segment-by-segment basis to determine whether microvascular integrity (contrast opacification score of 1 or 2) could predict contractile reserve (any improvement during low dose dobutamine infusion) in segments that were akinetic at rest. Follow-up echocardiography was performed one month later. RESULTS: Ninety-four (31%) of the 304 segments were akinetic at rest, and 22 (23%) of these demonstrated contractile reserve. In 87 (92%) of the resting akinetic segments contrast opacification could be adequately determined, and of these 20 (23%) showed microvascular integrity. The negative and positive predictive value of microvascular integrity for determining contractile reserve was 90% and 65%, respectively, and 92% and 59% respectively for predicting recovery of function. CONCLUSION: Power pulse inversion can be used at rest to determine myocardial function and simultaneously to predict contractile reserve of akinetic segments in patients early after myocardial infarction. This technique has the potential to provide a bedside assessment of myocardial viability.

Aged↗

PubMed1999

Acoustically stimulated transient power scattering explains enhanced detection of the very low velocities in myocardial capillaries by power Doppler imaging: an in vitro study.

BACKGROUND: Although enhanced detection of myocardial perfusion signals by power Doppler imaging during contrast echocardiography has been noted, flow velocities in the coronary microvasculature should generally be below the threshold for Doppler motion detection. It has been suggested that in this situation nonlinear scattering related to acoustically stimulated microsphere oscillation or destruction may be responsible for the detected Doppler shift. METHODS AND RESULTS: This study examined the behavior of MRX 115 (ImaRx Pharmaceuticals) microbubbles during harmonic and nonharmonic power Doppler imaging at varying power outputs (mechanical indexes 0. 3, 0.5, 0.7, and 0.9) in a perfusion tube model under zero-flow conditions. Boluses of MRX 115 0.5-mL suspension were introduced into the model, and flow was halted during each imaging period. Once power Doppler imaging was implemented, a signal was detected as unique sparkling color pixels corresponding to individual bubble destruction events, even in the absence of contrast movement. This phenomenon continued until all contrast bubbles disappeared from the region subjected to power Doppler imaging, usually within 35 to 40 seconds. Off-line videointensity measurements showed that initial power Doppler signal intensity and maximum signal decay rates increased parallel to increasing power output and were substantially greater for nonharmonic than for harmonic imaging modes. CONCLUSION: This relationship between signal intensity and decay rate and acoustic power output suggests that transient scattering related to bubble destruction is responsible for generation of the power Doppler signal in the absence of flow. This would explain the enhanced detection of the very low velocity flows in the myocardial capillaries by power Doppler contrast imaging.

Blood Flow Velocity↗

PubMed2000

Development of intrapulmonary arteriovenous shunting in postoperative biliary atresia: evaluation by contrast-enhanced echocardiography.

PURPOSE: This report presents biliary atresia (BA) patients with intrapulmonary arteriovenous shunting (IPS), which was evaluated suitably by contrast-enhanced echocardiography (CEC). METHODS: Of 88 BA patients seen in the last 20 years, 8 (9.1%) had IPS at 8 months to 16 years of age. Two were associated with polysplenia syndrome, 1 had persistent jaundice after hepatic portoenterostomy, and 2 underwent splenorenal shunt. According to the comparison between microbubbles in left atrium (LA) and in right atrium (RA) detected by CEC, IPS was classified as grade I, mild (LA << RA); grade II, moderate (LA < RA); grade II, severe (LA = RA). RESULTS: Grade I consisted of 4 patients whereas grade II and III held 2 patients each. Clinical symptoms such as cyanosis, exertional dyspnea, or clubbing were present in 50% of grade I and all of grade II and IlI. Mean PaO2 in grade I, II, and III was 70.5, 50.4, and 35.3 mm Hg, respectively. In 1 patient with grade I, IPS spontaneously disappeared, but pulmonary hypertension developed later. One patient in grade II died of pulmonary complications, and the other is considered a candidate for livertransplantation (LTx). One patient in grade III died of liver failure, whereas the other is free of IPS after LTx. CONCLUSION: IPS can lead to a life-threatening complication in postoperative BA patients, and CEC may be a convenient and useful method to evaluate the degree of IPS and determine therapeutic strategy.

Adolescent↗