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Cerebral microemboli during left heart catheterization.

BACKGROUND: The aim of this study was to describe the rate of microemboli signals (MES) during left heart catheterization (LHC). METHODS: A monitoring of both middle cerebral arteries using transcranial Doppler ultrasonography was performed to investigate cerebral microemboli during LHC. Seventy-two patients undergoing LHC and 29 patients with LHC followed by coronary intervention were studied. RESULTS: During a standardized LHC (n = 52), 95 +/- 45 MES were detected of which 67.5% occurred during injection of contrast media or saline solution, 30% during movements of wire and catheter, and 2% during catheter manipulation. During coronary interventions only, rotablation (n = 2) was followed by a massive increase in MES. The use of injection fluids prepared with minor gas content reduced the MES rate by 67% (P <.05). All MES were clinically silent. CONCLUSIONS: Cerebral microembolism is a current finding during LHC. The dependence of the MES rate during diagnostic LHC on the gas content of the injection fluids provides evidence that most of the MES are caused by microbubbles and not by solid emboli. The high rate of MES during coronary rotablation may be explained by the formation of cavitation bubbles. The clinical results of the MES during LHC appear to be benign.

Adult↗

Diagnostic efficacy of SonoVue.

SonoVue is a second-generation ultrasound contrast agent consisting of phospholipid-stabilized microbubbles filled with sulfur hexafluoride, with outstanding stability and resistance to pressure. The efficacy of SonoVue (0.5, 1, 2, 4 mL) was compared with Albunex (doses 0.08 and 0.22 mL/kg) in patients with suspected ischemic disease and suboptimal endocardial-border delineation on unenhanced echocardiography at rest. All the doses resulted in significantly greater increases compared with Albunex in left-ventricular endocardial-border delineation score as well as in the duration of clinically useful contrast effect. The utility of SonoVue in diagnosing ischemic heart disease was also evaluated during pharmacologic stress (arbutamine or dobutamine). SonoVue produced significant increases from baseline in endocardial-border delineation score both at rest and during pharmacologic stress. The possibility of detecting myocardial perfusion defects using SonoVue-enhanced power Doppler and gray-scale harmonic contrast echocardiography associated with continuous and intermittent imaging was assessed in patients with coronary artery disease. The results obtained were comparable with corresponding 99mTc sestamibi single-photon emission computed tomography images. An effective cardiovascular assessment of a patient should also include the evaluation of carotid vessels, intracranial circulation, and renal arteries. SonoVue provided significant improvements in the evaluation of the Doppler signal in terms of diagnosis agreement with reference imaging modality especially for intracranial vessels. The safety profile of SonoVue was evaluated in 1,406 patients. The incidence of adverse events was 10.4%, the great majority of which were of mild intensity and resolved without consequences.

Albumins↗

Comparison of four echocardiographic techniques for measuring left ventricular ejection fraction.

Accurate quantitative measurement of left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography is limited by subjective visual endocardial border detection. Both harmonic and precision contrast microbubbles provide better delineation of endocardial borders than fundamental imaging. The aim of this study was to correlate 2-dimensional echocardiographic quantification of LVEF measured by 4 currently available techniques with radionuclide angiography. A total of 50 patients who underwent radionuclide (EF) measurement (47 of 50 had technically difficult echocardiograms by fundamental imaging) underwent echocardiography by 4 methods: fundamental alone, fundamental with contrast, harmonic alone, and harmonic with contrast. Three echocardiologists measured the biplane 2-dimensional echocardiographic LVEF independently and were blinded to radionuclide angiography. The correlation of echocardiographic EF with radionuclide EF improved incrementally with each method. However, contrast with harmonic imaging provided the closest correlation (r = 0.95, 0.96, and 0.95 as assessed by the 3 independent analysts.

Adult↗

Usefulness of power Doppler contrast echocardiography to identify reperfusion after acute myocardial infarction.

Microvascular integrity, as seen by myocardial contrast echocardiography (MCE), assesses whether myocardium has been successfully reperfused after an acute myocardial infarction. Until now this has been demonstrated only with intracoronary injection of an ultrasound contrast agent. Power Doppler imaging is a recently developed myocardial contrast echocardiographic method that counts the contrast microbubbles destroyed by ultrasounds and displays this number in color. This study sought to evaluate whether power Doppler MCE is able to visualize myocardial reperfusion during intravenous contrast injection. Thirty patients were evaluated 2 days after their first myocardial infarction during intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA). Coronary artery angiography and single-photon emission computed tomography (SPECT) were used as reference techniques. A 16-segment left ventricular model was used to relate perfusion to coronary artery territories. Sensitivity and specificity of power Doppler MCE for segments supplied by infarct-related arteries were 82% and 95%, respectively. Accuracy of power Doppler MCE and SPECT were similar (90% vs 92% on segmental basis and 98% vs 98% on coronary artery territory basis). Two-dimensional echocardiography was repeated after 6 weeks. Segments recovering wall motion after 6 weeks were defined as stunning myocardium. Dysfunctional but perfused myocardium at day 2 after the infarction showed a better late recovery of wall motion compared with dysfunctional but nonperfused myocardium (p <0.001). In conclusion, harmonic power Doppler imaging is a sensitive and specific method for the identification of myocardial reperfusion early after myocardial infarction. It yields prognostic information for late recovery of ventricular function differentiating stunning (dysfunctional but perfused) from necrotic myocardium (dysfunctional and nonperfused).

Adult↗

Usefulness of myocardial contrast echocardiography using low-power continuous imaging early after acute myocardial infarction to predict late functional left ventricular recovery.

Microvascular perfusion is a prerequisite for ensuring viability early after acute myocardial infarction (AMI). For adequate assessment of myocardial perfusion, both myocardial blood volume and velocity need to be evaluated. Due to its high frame rate, low-power continuous myocardial contrast echocardiography (MCE) can rapidly assess these parameters of myocardial perfusion. We hypothesized that the technique can accurately differentiate necrotic from viable myocardium after reperfusion therapy in AMI. Accordingly, 50 patients underwent low-power continuous MCE using intravenous Optison (Amersham Health, Amersham, Middlesex, United Kingdom) 7 to 10 days after AMI. Myocardial perfusion (contrast opacification assessed over 15 cardiac cycles after the destruction of microbubbles with high energy pulses) and wall thickening were assessed at baseline. Regional and global left ventricular (LV) function was reassessed after 12 weeks. Out of the 297 dysfunctional segments, MCE detected no contrast enhancement during 15 cardiac cycles in 172 segments, of which 160 (93%) failed to show improvement. MCE demonstrated contrast opacification during 15 cardiac cycles in 77 segments, of which 65 (84%) showed recovery of function. The greater the extent and intensity of contrast opacification, the better the LV function at 3 months (p <0.001, r = -0.91). Almost all patients (94%) with <20% perfusion in dysfunctional myocardium (assessing various cut-offs) failed to demonstrate an improvement in LV function. MCE and peak creatine kinase proved to be independent predictors of functional recovery (p <0.001). In conclusion, low-power continuous MCE is an accurate and rapid bedside technique to identify microvascular perfusion after AMI. This technique may be utilized to reliably predict late recovery of function in dysfunctional myocardium after AMI.

Aged↗

Comparison of intravenous myocardial contrast echocardiography and low-dose dobutamine echocardiography for predicting left ventricular functional recovery following acute myocardial infarction.

Akinesia after acute myocardial infarction (AMI) may be reversible or irreversible. Distinguishing these 2 entities early after AMI is difficult, but clinically important. Previous studies have shown that myocardial contrast echocardiography (MCE) and low-dose dobutamine echocardiography (DE) may both be useful in this setting. However, there are few data regarding the relative and combined value of these techniques. The aim of this study was to compare the utility of real-time intravenous MCE and low-dose DE in the early prediction of functional recovery of akinetic myocardium after AMI. Thirty-seven patients were studied 3 +/- 2 days after an AMI. Each subject underwent real-time MCE using an intravenous infusion of perflutren microbubbles. Immediately after this, low-dose DE was performed. Contrast opacification and wall motion were determined by experienced observers blinded to clinical data. Repeat echocardiograms were obtained 51 +/- 19 days later and wall motion at rest was scored by an observer blinded to clinical data. Normal contrast opacification predicted functional recovery with a positive predictive value of 63%, a negative predictive value of 73%, and an accuracy of 66%. Residual contractility during low-dose DE had a positive predictive value of 82%, a negative predictive value of 72%, and a predictive accuracy of 76%. When the 2 tests were concordant (64%), they had a positive predictive value of 81%, a negative predictive value of 85%, and a predictive accuracy of 83%. Low-dose DE was superior to intravenous MCE in the prediction of functional recovery of akinetic myocardium after AMI, but the combination of both maximizes predictive accuracy.

Aged↗

Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings.

Transesophageal echocardiography (TEE) is accepted as the method of choice for the diagnosis of the patent foramen ovale (PFO). However, direct anatomic confirmation regarding the presence or absence of a PFO on transesophageal imaging has been obtained in only a limited number of patients. Consequently, this study was performed to assess the diagnostic accuracy of contrast and color Doppler TEE for detection of a PFO by comparing the results of TEE with autopsy. The study population comprised 35 consecutive patients (mean age 64 +/- 14 years) who underwent autopsy and prior TEE with examination of the atrial septum. For diagnosis of a PFO, the following criteria were used: (1) no defect in the continuity of the atrial septum on 2-dimensional imaging; (2) > or = 1 bright microbubble appearing in left the atrium within 3 heart cycles after opacification of the right atrium during contrast TEE; and (3) turbulent color jet within the atrial septum by color Doppler TEE. For estimating the PFO size, positive contrast studies were graded semiquantitatively (from 1 to 3), and the maximal color Doppler jet width was measured within the atrium septum at the area of maximal turbulence. At autopsy, a PFO was present in 9 of 35 patients (26%). All were correctly diagnosed by color Doppler TEE. The color Doppler jet width correlated well with the PFO diameter determined at autopsy (r=0.99, SEE=0.51 mm, p<0.0001). By contrast TEE, 8 of the 9 patients with autopsy-proven PFO were correctly identified. In 1 case with left heart disease and a long interatrial channel, a PFO was missed by contrast TEE but clearly demonstrated by color Doppler TEE. All patients with a PFO diameter >10 mm showed intense left atrial opacification of grade 3. With both methods, there were no false-positive results. Sensitivity and specificity for diagnosis of a PFO were 89% and 100% respectively, for contrast TEE, and both 100% for color Doppler TEE. Thus, contrast and color Doppler TEE are complementary and represent a highly sensitive and specific method for diagnosis of a PFO and for estimation of the PFO size.

Adult↗

Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction.

Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.

Angioplasty, Balloon, Coronary↗

Cerebral microembolism during carotid endarterectomy.

BACKGROUND: This study was designed to assess the intraoperative risk of cerebral microembolism, as detected by transcranial Doppler ultrasonography, during carotid endarterectomy. PATIENTS AND METHODS: Thirty-six patients (37 procedures) with symptomatic (n = 35) or asymptomatic (n = 2) internal carotid artery origin stenosis(> 50%) were monitored continuously during carotid endarterectomy. Special instrumentation was used to detect high-intensity transient signals (HITS) in the middle cerebral artery on the carotid endarterectomy side. All HITS satisfied a priori established criteria. RESULTS: The incidence of carotid endarterectomies with formed-element HITS increased at clamp release (23/37, P < 0.001) and shunt opening (7/11, P = 0.014), and during wound closure (13/22, P< 0.005) and shunting (5/11, P = 0.046). HITS with air microbubble characteristics were detected at clamp release (22/37, P < 0.001) and shunt opening (5/11, P = 0.025). CONCLUSIONS: HITS do not occur randomly during carotid endarterectomy. Shunting, unclamping, and wound closure are high-risk periods.

Aged↗

Quantification methods.

Ultrasound contrast agents can be assimilated to intravascular flow tracers opening the field of myocardial blood flow (MBF) quantification. However, tracer theories are invalidated because of microbubble unstable structure and peripheral injection. In order to overcome these limitations, new models have been developed as destruction/refilling sequences allowing MBF assessment.

Contrast Media↗

Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study.

BACKGROUND: We evaluated distribution of warm antegrade and retrograde cardioplegia in patients undergoing coronary artery bypass grafting (CABG). METHODS: Myocardial perfusion was evaluated pre- and post-CABG using transesophageal echocardiography with injection of sonicated albumin microbubbles (Albunex) during warm antegrade and retrograde cardioplegia. The left ventricle (LV) was evaluated in five segments and the right ventricle (RV) was evaluated in two segments. Segmental contrast enhancement was graded as absent (score = 0), suboptimal or weak (score = 1), optimal or excellent (score = 2), or excessive (score = 3). RESULTS: Pre-CABG cardioplegic perfusion correlated weakly with severity of coronary artery stenoses (r = -0.331 and 0.276 for antegrade and retrograde cardioplegia, respectively). Antegrade cardioplegia administration resulted in 98% and 96% perfusion to the left ventricle pre- and post-CABG, respectively. Retrograde cardioplegic administration resulted in reduced LV perfusion, with 86% (p = 0.032 from antegrade) and 59% (p<0.001 from antegrade) pre- and post-CABG, respectively. The average LV perfusion score (mean +/- SEM) was greater with antegrade than retrograde cardioplegia both pre-CABG (1.93+/-0.04 vs. 1.53+/-0.11, p<0.001) and post-CABG (1.63+/-0.07 vs. 1.19+/-0.13, p = 0.004). RV perfusion was poor with both techniques pre-CABG, but improved significantly with antegrade cardioplegia post-CABG. CONCLUSIONS: We conclude that warm antegrade cardioplegia results in better left ventricular perfusion than warm retrograde cardioplegia. Right ventricular cardioplegic perfusion was suboptimal, but the best delivery was achieved with antegrade cardioplegia after coronary bypass. We therefore recommend construction of the saphenous vein graft to the right coronary artery early in the operative procedure.

Aged↗

Carbonate interferences by ion chromatographic determination of anions in mineral waters.

The high content of hydrogen carbonate anions and dissolved CO2 in some mineral waters interfere with the determination of anions in such samples by ion chromatography. It was found that the irreproducibility of retention times of all anions present in the samples was caused by on-column neutralisation of CO(3)2- to HCO3- by CO2. Microbubbles of CO2 released downstream by the suppressor inhibited exchange of Na+ with H3O+ resulting in lower conductivity and consequently in the decrease of chloride peak. To avoid peak deformation and overlapping caused by carbonate species, they should be removed by acidification followed by CO2 elimination in a gas separation unit. To prevent sample contamination by the anion of the added acid, the electrodialytic clean-up procedure was applied. The liberated CO2 was removed in a microporous Gore-Tex semipermeable tubing connected in series with the dialytic cell. The developed dialytic clean-up procedure was applied to the analysis of some typical mineral waters.

Anions↗

The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass.

OBJECTIVE: Neuropsychologic disorders are common after coronary artery bypass operations. Air microbubbles are identified as a contributing factor. A dynamic bubble trap might reduce the number of gaseous microemboli. METHODS: A total of 50 patients undergoing coronary artery bypass operation were recruited for this study. In 26 patients a dynamic bubble trap was placed between the arterial filter and the aortic cannula (group 1), and in 24 patients a placebo dynamic bubble trap was used (group 2). The number of high-intensity transient signals within the proximal middle cerebral artery was continuously measured on both sides during bypass, which was separated into 4 periods: phase 1, start of bypass until aortic clamping; phase 2, aortic clamping until rewarming; phase 3, rewarming until clamp removal; and phase 4, clamp removal until end of bypass. S100 beta values were measured before, immediately after, and 6 and 48 hours after the operation and before hospital discharge. RESULTS: The bubble elimination rate during bypass was 77% in group 1 and 28% in group 2 (P <.0001). The number of high-intensity signals was lower in group 1 during phase 1 (5.8 +/- 7.3 vs 16 +/- 15.4, P <.05 vs group 2) and phase 2 (6.9 +/- 7.3 vs 24.2 +/- 27.3, P <.05 vs group 2) but not during phases 3 and 4. Serum S100 beta values were equally increased in both groups immediately after the operation. Group 2 patients had higher S100 beta values 6 hours after the operation and significantly higher S100 beta values 48 hours after the operation (0.06 +/- 0.14 vs 0.18 +/- 0.24, P =.0133 vs group 2). Age and S100 beta values were correlated in group 2 but not in group 1. CONCLUSION: Gaseous microemboli can be removed with a dynamic bubble trap. Subclinical cerebral injury detectable by increases of S100 beta disappears earlier after surgical intervention.

Aged↗

Etiology, screening, and treatment of hepatocellular carcinoma.

The prognosis with large hepatocellular carcinomas is poor, and only palliative treatment is available. Small tumors are amenable to several modes of treatment, including liver transplantation, resection, or alcohol injection, with acceptable 5-year survival rates. Although the value of screening for hepatocellular carcinoma has yet to be shown, these data, coupled with the recognition of at-risk groups and useful diagnostic techniques, might encourage the clinician to screen at-risk patients in the clinic. New imaging techniques such as ultrasonographic angiography enhanced with CO2 microbubbles, or color Doppler ultrasound, may clarify the intratumoral blood flow of small tumors.

Biomarkers, Tumor↗

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria.

To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

Adult↗

Etiology of cecal and hepatic lesions in mice after administration of gas-carrier contrast agents used in ultrasound imaging.

The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.

Albumins↗

Clinical applications of ultrasound contrast agents.

Within the last decade safe and practical ultrasound contrast agents have been introduced. Most of these are based on gas-filled microbubbles, which markedly enhance Doppler signals and, in some cases, also gray-scale images. The clinical improvements expected from ultrasound contrast is reviewed. Tissue-specific contrast agents constitute another area of potential clinical significance. One particular agent is taken up by the reticulo-endothelial system and produces so-called acoustic emission signals when imaged. An introduction to the unique clinical applications of acoustic emission is given. Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of some agents in an attempt to alleviate current limitations of ultrasound contrast studies. Examples of harmonic images are presented.

Acoustics↗

Subharmonic imaging of contrast agents.

Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.

Acoustics↗