Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion

Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion.     

Clinical applications of transpulmonary contrast echocardiography

BACKGROUND: The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging. METHODS AND RESULTS: This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents. CONCLUSIONS: New intravenous contrast agents offer the possibility to assess myocardial perfusion echocardiographically. It is also possible to use these agents for delivery of therapeutic agents, including gene therapy.     

Assessment of left ventricular volume by contrast echocardiography

Two-dimensional echocardiography for measuring left ventricular volumes usually gives volumes that are smaller than those determined with left ventriculography. This is due to less optimal image quality since manual tracing of endocardial borders requires still frames. Intravenous injection of echocontrast agent (Albunex) improve endocardial border recognition and therefore left ventricular volume measurements become more accurate. It is reported that contrast echocardiography significantly improves the correlation of echocardiographic left ventricular volume measurement with that of left ventriculography. From this points of view, contrast echocardiography is useful for the determination of left ventricular volumes in clinical settings.     

Identification of atrial septal defects by cross-sectional contrast echocardiography

Cross-sectional echocardiography, combined with injections of contrast into peripheral arm veins, has been used to study 15 patients with atrial septal defects and 10 patients with an intact interatrial septum. Of 11 patients with ostium secundum or sinus venosus atrial septal defects and left-to-right shunts a defect could be visualised in all, and in eight some degree of transfer of contrast from right atrium to left atrium was seen. In three of four patients with a dominant right-to-left shunt a defect was seen and in all there was free transfer of contrast from right atrium to left atrium. Though there may be variable loss of echoes in the septal image in patients with an intact interatrial septum, in general no fixed defect is seen an there is no transfer of contrast from right atrium to left atrium. This is a potentially valuable technique in the assessment of patients in whom an atrial septal defect is suspected.     

Transesophageal echocardiography in the detection of cardiovascular sources of peripheral vascular embolism

The purpose of this study was to determine the impact of transesophageal echocardiography (TEE) on the management of patients with peripheral vascular emboli. We prospectively evaluated the role of TEE in 15 patients with documented peripheral emboli and no evidence of occlusive peripheral vascular disease. The patients were divided in two groups for analysis: group 1 (n = 8) had no clinical evidence of heart disease and group 2 (n = 7) had clinically significant heart disease. TEE provided information regarding the source of embolism in four (50%) patients in group 1, and these findings significantly affected the management of all. Three patients underwent thoracic surgery to remove the source of embolism (aortic valve mass in one and a thrombus in the descending thoracic aorta in two); the other patients was treated with thrombolytic agents. TEE findings had high diagnostic value in all patients in group 2, but the results had a possible effect on clinical management in only two of these patients. TEE provides diagnostic information in most patients with peripheral vascular emboli and this information has a significant influence on management, particularly in those without clinically evident heart disease. TEE should be performed in all patients with documented peripheral embolism.     

Assessment of transmural distribution of myocardial perfusion with contrast echocardiography

BACKGROUND: We hypothesized that by using our newly defined method of destroying microbubbles and measuring their rate of tissue replenishment, we could assess the transmural distribution of myocardial perfusion. METHODS AND RESULTS: We studied 12 dogs before and after creation of left anterior descending coronary artery stenoses both at rest and during hyperemia (n=62 stages). Microbubbles were administered as a constant infusion, and myocardial contrast echocardiography (MCE) was performed with the use of different pulsing intervals. The video intensity versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y=A(1-ebetat), where A reflects microvascular cross-sectional area (or myocardial blood volume), and beta reflects mean myocardial microbubble velocity. The product A . beta represents myocardial blood flow (MBF). Average values for these parameters were derived from the endocardial and epicardial regions of interest placed over the left anterior descending coronary artery bed. Radiolabeled microsphere-derived MBF was also measured from the same regions. There was poor correlation between radiolabeled microsphere-derived MBF and A-endocardial/epicardial ratios (EER) (r=0.46). The correlation with beta-EER was better (r=0. 69, P<0.01). The best correlation with radiolabeled microsphere-derived MBF-EER was noted with A . beta-EER (r=0.88, P<0. 01). CONCLUSIONS: The transmural distribution of myocardial perfusion can be accurately assessed with MCE with the use of our newly described method of tissue replenishment of microbubbles after their ultrasound-induced destruction. In the model studied, an uncoupling of the transmural distribution of MBF and myocardial blood volume was observed during reversal of the MBF-EER.     

Anxiety and depressive disorders in cardiovascular diseases

Cardiovascular diseases are often associated with anxiety and depression. The literature gives different interpretations of this comorbidity. Psychopathological factors have been successively studied as risk factors, comorbid disorders and factors influencing the prognostic. The authors describe the incidence and the prevalence of anxiety and depression, first in coronary heart disease and secondly before cardiac surgery. The prognostic significance of these psychological factors is also reviewed. Physiopathological hypothesis and practical application in clinical practice are proposed.     

Potential advantage of flash echocardiography for digital subtraction of B-mode images acquired during myocardial contrast echocardiography

Optimal assessment of myocardial perfusion with contrast echocardiography by using B-mode imaging often requires image alignment and background subtraction, which are time consuming and need extensive expertise. Flash echocardiography is a new technique in which primary images are gated to the electrocardiogram and secondary images are obtained by transmitting ultrasound pulses in rapid succession after each primary image. Myocardial opacification is seen in the primary image and not in the secondary images because of ultrasound-induced bubble destruction. Because the interval between the primary and first few secondary images is very short, cardiac motion between these images should be minimal. Therefore we hypothesized that 1 or more secondary images could be subtracted from the primary image without the need for image alignment. The ability of ultrasound to destroy microbubbles was assessed by varying the sampling rate, line density, and mechanical index in 6 open-chest dogs. The degree of translation between images was quantified in the x and y directions with the use of computer cross-correlation. At sampling rates of 158 Hz or less and a mechanical index of more than 0.6, videointensity rapidly declined to baseline levels by 25 ms. Significant translation between images was noted only at intervals of more than 112 ms. It is concluded that flash echocardiography can be used for digital subtraction of baseline from contrast-enhanced B-mode images without image alignment. Background subtraction is therefore feasible on-line, potentially eliminating the need for off-line image processing in the future.     

Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 microns average microbubble size, concentration 8 x 8(8)/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial blood flow changes and showed a significant correlation with radiolabeled microspheres (r = 0.65, p = 0.0001).     

Preoperative diagnosis of a patent foramen ovale: rational use of transthoracic and transesophageal contrast echocardiography

BACKGROUND: The detection or ruling out of a patent foramen ovale (PFO) can be determined noninvasively by contrast echocardiography (CE). The transesophageal technique is superior to the transthoracic technique regarding sensitivity, whereas the specificity of both methods is equally high. This prospective study shows the rational use of transesophageal CE for the detection of a PFO, in patients without cardiovascular disorders. METHODS: 165 patients (92 female, 73 male, age 48 +/- 18 years) with planned neuro-surgery in a sitting position, underwent CE to rule out a PFO. If the CE was positive, an alternative position was selected in order to avoid a paradoxical air embolism. RESULTS: Initially, a transthoracic CE was performed in all patients resulting in 21 patients (13%) being positive and 39 patients (24%) being negative by sufficient image quality. A transesophageal CE was performed in 96 of the remaining 105 patients (63%). Here, further 25 patients showed a positive CE in the sense of a PFO. The combined use of transthoracic and transesophageal CE revealed a PFO in 46 of 165 patients (28%). CONCLUSION: The use of both, transthoracic and transesophageal CE is an efficient approach to the preoperative detection of a PFO in the sense of quality and economics. Depending upon the image quality, the use of a transesophageal examination could be avoided in one third of the cases.     

Myocardial contrast echocardiography in acute myocardial infarction. Pathophysiological background and clinical applications

Myocardial contrast echocardiography is a technique used in experimental and clinical settings in order to visualize the pattern of intramyocardial perfusion. In the acute phase of myocardial infarction, regional absence of flow during myocardial contrast echocardiography delineates the area at risk of necrosis, while the definitive non-perfused area expresses infarct size. Reopening the infarct-related artery, which may be achieved spontaneously by thrombolysis or percutaneous transluminal coronary angioplasty, is not a reliable indicator of intramyocardial reperfusion. If myocardial ischaemia due to coronary occlusion has been sufficiently prolonged and severe, not only myocyte viability, but also microvascular integrity is lost. Myocardial contrast echocardiography, using intracoronary injection of sonicated contrast medium, gives information about microvascular integrity and the effective presence of intramyocardial reflow. Anatomical integrity of microvasculature does not necessarily imply preserved function, and thus the microvessel vasodilating reserve may also be impaired. Myocardial contrast echocardiography has the potential to assess alterations in microvascular function, showing, in the myocardial area with reduced coronary reserve, a relatively reduced increase in echocontrast signal intensity when an intravenous vasodilator agent is administered.     

Visualization and quantification of myocardial mass at risk using three-dimensional contrast echocardiography

To investigate possible biochemical mechanisms underlying the "toxic gain of function" associated with polyglutamine expansions, the ability of guinea pig liver tissue transglutaminase to catalyze covalent attachments of various polyamines to polyglutamine peptides was examined. Of the polyamines tested, spermine is the most active substrate, followed by spermidine and putrescine. Formation of covalent cross links between polyglutamine peptides and polyamines yields high-M(r) aggregates--a process that is favored with longer polyglutamines. In the presence of tissue transglutaminase, purified glyceraldehyde-3-phosphate dehydrogenase (a key glycolytic enzyme that binds tightly to the polyglutamine domains of both huntingtin and dentatorubral-pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides in vitro, resulting in the formation of high-M(r) aggregates. In addition, endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast cell line overexpressing human tissue transglutaminase forms cross-links with a Q60 polypeptide added to the cell homogenate. Possibly, expansion of polyglutamine domains (thus far known to occur in the gene products associated with at least seven neurodegenerative diseases) leads to increased/aberrant tissue transglutaminase-catalyzed cross-linking reactions with both polyamines and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase. Formation of cross-linked heteropolymers may lead to deposition of high-M(r) protein aggregates, thereby contributing to cell death.     

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection

BACKGROUND: The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. METHODS AND RESULTS: Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P < .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. CONCLUSIONS: Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.     

Review of Childhood disorders: Behavioral-developmental approaches.

Reviews the book, Childhood disorders: Behavioral-developmental approaches edited by Robert J. McMahon and Ray Dev. Peters (1985). This volume includes 11 original chapters from the 1983 Banff International Conference on Behavioral Sciences. Together, these chapters provide an overview of a number of high-quality programmes of research in the area of childhood disorders. The editors state that the purpose of the current offering is to focus on recent advances in the conceptualization, assessment, and treatment of childhood behaviour disorders, with particular attention being given to the role of developmental processes. The book contains two major sections. The first provides an overview of the conceptual foundations for a "behavioural-developmental" approach to childhood disorders. The second, which constitutes approximately 80% of the volume, illustrates programmes for the assessment and treatment of childhood disorders spanning the developmental spectrum from infancy to adolescence. Although this volume's attempt to bridge the gap between behavioural and developmental work may fall short, it is nevertheless a worthwhile contribution that nicely illustrates a range of outstanding programmes of clinical research for a variety of childhood disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improved quantification of myocardial mass by three-dimensional echocardiography using a deposit contrast agent

Adhesion-dependent cell signaling is known to be important in carcinogenesis. It is postulated that several types of adhesion molecules act as tumor suppressor genes by enforcing cell-substrate and cell-cell adhesion thereby preventing the migration of cells and their invasion into surrounding tissues. Recent evidence, however, suggests that disruption of adhesion systems can both initiate neoplastic transformation and contribute a rate-limiting step to progression. Adhesion may modulate neoplastic processes by altering pathways that control genomic stability. Analysis of the adhesion-controlled inactivation of the p53 protein and the concomitant relaxation of cell cycle checkpoint control could identify the critical contributions of adhesion-mediated influences to carcinogenesis.