What is normal oesophageal motility? An ambulatory study

BACKGROUND: Ultrasound can cause microbubble destruction. If microbubbles are administered as a continuous infusion, then their destruction within the myocardium and measurement of their myocardial reappearance rate at steady state will provide a measure of mean myocardial microbubble velocity. Conversely, measurement of their myocardial concentration at steady state will provide an assessment of microvascular cross-sectional area. Myocardial blood flow (MBF) can then be calculated from the product of the two. METHODS AND RESULTS: Ex vivo and in vitro experiments were performed in which either flow was held constant and pulsing interval (interval between microbubble destruction and replenishment) was altered, or vice versa. In vivo experiments were performed in 21 dogs. In group 1 dogs (n=7), MBF was mechanically altered in a model in which coronary blood volume was constant. In group 2 dogs (n=5), MBF was altered by direct coronary infusions of vasodilators. In group 3 dogs (n=9), non-flow-limiting coronary stenoses were created, and MBF was measured before and after the venous administration of a coronary vasodilator. In all experiments, microbubbles were delivered as a constant infusion, and myocardial contrast echocardiography was performed using different pulsing intervals. The myocardial video intensity versus pulsing interval plots were fitted to an exponential function: y=A(1-e[-betat]), where A is the plateau video intensity reflecting the microvascular cross-sectional area, and beta reflects the rate of rise of video intensity and, hence, microbubble velocity. Excellent correlations were found between flow and beta, as well as flow and the product of A and beta. CONCLUSIONS: MBF can be quantified with myocardial contrast echocardiography during a venous infusion of microbubbles. This novel approach has potential for measuring tissue perfusion in any organ accessible to ultrasound.     

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of "perfusion." Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings.     

Harmonic imaging

Microbubbles undergoing resonant oscillation in a diagnostic ultrasound field can be induced to exhibit nonlinear motion. The ultrasound signals emitted by such microbubbles contain strong harmonics at twice the frequency of the transmitted ultrasound beam. Second harmonic imaging improves tissue-agent contrast. The usefulness of second harmonic imaging was evaluated in vivo experiments. The hepatic parenchyma was clearly enhanced in dogs. Second harmonic imaging can be expected to expand the capabilities of diagnostic ultrasound systems in visualizing tissue perfusion.     

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.     

Computerised infrared imaging system for studying thermal activation on the skull following somatic stimulation in small animals

Stress radionuclide myocardial perfusion imaging and stress echocardiography are noninvasive imaging techniques with high diagnostic and prognostic utility. Previously, patient cohorts for studies using these methods have comprised predominantly men, but recent investigations have focused on women. Stress myocardial perfusion imaging is highly accurate for diagnosing coronary disease in women, particularly with newer techniques such as gated single-photon emission computed tomography, and has been shown to be a powerful prognostic predictor in both women and men. Comparable data for stress echocardiography are emerging. Older studies reported that for similar image findings fewer women than men were referred for invasive procedures, however, newer studies suggest an absence of such a gender bias. Further developments in attenuation correction for perfusion imaging and phase-contrast magnetic resonance imaging promise to enhance the utility of noninvasive imaging for both men and women.     

Tissue Doppler imaging and the quantification of myocardial function

Tissue Doppler imaging (TDI) has recently been introduced in clinical echocardiography. Most widely used are tissue velocity maps, in which the velocity of moving tissue is calculated relative to the transducer from the Doppler shift and displayed as colour-encoded velocity maps in either M-mode or two-dimensional image formats (Doppler velocity mode). This allows detection and quantification of dyssynergic areas of the myocardium. Additionally, the velocities may be studied with pulsed wave-tissue Doppler sampling (PW-TDS) which displays the velocity of a selected myocardial region versus time with high temporal resolution. Less often used, are tissue acceleration maps which display acceleration or velocity change of subsequent frames as different colours (Doppler acceleration mode). These maps may find application in clinical electrophysiology. Another TDI modality is tissue energy imaging, which is based on the integration of the power spectrum of the Doppler signals from the tissue. This technique provides maps of Doppler energy which are represented as colour brightness. Such maps offer potential for the study of myocardial perfusion. TDI modalities have promise to become clinically useful for quantifying myocardial function.     

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.     

Evaluation of pulmonary vascular anatomy and blood flow by magnetic resonance

Rapidly evolving magnetic resonance (MR) imaging techniques provide noninvasive approaches to evaluating morphology and quantitative physiologic information about blood flow in the pulmonary circulation. Important clinical applications currently include the preoperative and postoperative evaluation of congenital abnormalities, assessment of vascular involvement by extrinsic and intrinsic tumors, identification of central thromboemboli, and diagnosis of vascular lung lesions. Ongoing refinements in pulmonary MR angiography may make it possible to use the technique for the noninvasive detection of acute pulmonary emboli in the near future. Quantitative measurements based upon MR flow-encoding sequences are promising for the evaluation of patients with abnormal degrees or distributions of pulmonary blood flow, for example, those with unilateral lung transplants or pulmonary arterial stenoses. MR contrast agents currently under development also show promise for quantitative measurements of regional pulmonary ventilation and perfusion. The coupling of high-resolution anatomic and functional images renders MR a uniquely attractive and powerful method for evaluating the pulmonary vasculature.     

Magnetic resonance imaging of perfusion in the isolated rat heart using spin inversion of arterial water

Measurement of regional myocardial perfusion is important for the diagnosis and treatment of coronary artery disease. Currently used methods for the measurement of myocardial tissue perfusion are either invasive or not quantitative. Here, we demonstrate a technique for the measurement of myocardial perfusion using magnetic resonance imaging (MRI) with spin tagging of arterial water. In addition, it is shown that changes in perfusion can be quantitated by measuring changes in tissue T1. Perfusion images are obtained in Langendorff-perfused, isolated rat hearts for perfusion rates ranging from 5 to 22 ml/g/min. The MRI-determined perfusion rates are in excellent agreement with perfusion rates determined from measurement of bulk perfusate flow (r = 0.98). The predicted linear dependence of the measured T1 (T1app) on perfusion is also demonstrated. The ability of perfusion imaging to measure regional variations in flow is demonstrated with hearts in which perfusion defects were created by ligation of a coronary artery. These results indicate that MRI of perfusion using spin inversion of arterial water gives quantitative maps of cardiac perfusion.     

Recent developments in the prognostic use of myocardial perfusion imaging

Stress myocardial perfusion imaging has become a mainstay in the noninvasive assessment of patients with known or suspected coronary artery disease for several compelling reasons. Radionuclide myocardial perfusion imaging can be performed using a variety of stressors, including exercise, pharmacologic stress (including dipyridamole, adenosine, dobutamine, and arbutamine), or a combination of exercise and pharmacologic stress. The combination of exercise and pharmacologic stress allows an assessment of the patient's exercise tolerance, to be performed while adequately stressing him or her pharmacologically. Radiopharmaceutical choice has been expanded to include not only thallium-201 but also technetium-based imaging agents such as sestamibi and tetrofosmin. The use of technetium imaging agents has recently been enhanced by the ability to assess ventricular function using gated single-photon emission computed tomography (SPECT) imaging techniques. Finally, the ability to provide prognostic information in the same patients has led to incremental clinical use.     

Dissolution of multicomponent microbubbles in the bloodstream: 2. Experiment

The effect of the nature of the filling gas on the persistence of microbubbles in the bloodstream was studied. All the microbubbles were covered with the same shells. Various perfluorocarbons and perfluoropolyethers alone and as mixtures with nitrogen were used as the filling gases. The persistence time of microbubbles in the bloodstream tau increased with the molecular weight of the filling gas, from approximately 2 min for perfluorethane, to > 40 min for perfluorodiglyme, C6F14O3, and then decreased again to 8 min for C6F14O5. An acceptable ultrasound scattering efficacy was exhibited by the filling gases with intermediate molecular weights that possessed both a high saturated vapor pressure and a comparatively low water solubility (Ostwald coefficient). On the basis of the experimental data, it is concluded that the microbubble persistence tau is controlled primarily by the dissolution of microbubbles and not by the removal of the microbubbles by the reticular endothelial system. Although the qualitative experimental trends are in good agreement with the theoretical model developed previously, there are some quantitative differences. Possible reasons for these differences are discussed.     

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.     

New approaches to resolving diagnostic problems in patients with angina pectoris

Several new noninvasive techniques are now available to evaluate the patient with chest pain to determine if myocardial ischemia is present. Continuous ambulatory ECG monitoring can detect myocardial ischemia in some patients who have normal ECG responses to graded exercise tests. Defects in myocardial perfusion can be visualized by radionuclide imaging at rest and after exercise. Also, abnormal left ventricular wall motion due to myocardial ischemia can be detected by gated blood pool scanning at the same time. Other techniques can olso be valuable in evaluating wall motion. Standard M-mode echocardiography can detect anteroseptal and posteroinferior wall motion abnormalities with remarkable anatomic detail, and newer echo techniques are promising for delineating the motion of other parts of the left ventricle. Finally, abnormal contractile areas can be assessed by videotracking the fluoroscopic cardiac silhouette and by a new noninvasive technique, the displacement cardiograph, which does not involve radiation exposure. Although none of these tests are both highly sensitive and highly specific for myocardial ischemia, their combined application in a symptomatic patient may provide considerable useful information which will help to determine who should be subjected to the risk and expense of coronary arteriography.     

Contrast echocardiography and myocardial perfusion: what is the current status?

Progress in the field of echocardiographic contrast agent combined with progress in imaging techniques (second harmonic imaging, intermittent imaging, Doppler Energy) should allow a real revolution in the field of noninvasive cardiac imaging, and one of the main advantages will probably be myocardial perfusion imaging in ischaemic heart disease.     

Albumin microbubble persistence during myocardial contrast echocardiography is associated with microvascular endothelial glycocalyx damage

BACKGROUND: We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury. METHODS AND RESULTS: The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K+ content, pH, PO2, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP. CONCLUSIONS: Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.     

Thallium-201 myocardial perfusion imaging in infants and children. Value in distinguishing anomalous left coronary artery from congestive cardiomyopathy

In infants and children, anomalous origin of the left coronary artery (ALCA) from the pulmonary artery may be difficult to distinguish from congestive cardiomyopathy (CCM) of other causes. We performed thallium-201 myocardial perfusion imaging in seven children with ALCA and in nine with CCM to study the usefulness of this technique in distinguishing between these lesions. Localized abnormalities of thallium uptake were present in each of the seven patients with ALCA, including two asymptomatic 4-year-old children. Thallium distribution was normal in five patients with CCM, diffusely irregular in three, and was absent in the lateral and posterobasal portions of the left ventricle in one patient. We conclude that thallium-201 imaging is a sensitive noninvasive method of detecting ALCA. However, perfusion abnormalities are not limited to patients with coronary artery abnormalities, and may be present in patients with myocardial ischemia or infarction of other causes.     

Correlation between quantitative angiographic lesion severity and myocardial contrast intensity during a continuous infusion of perfluorocarbon-containing microbubbles

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = -0.89 for both, p<0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography.     

Methods for coronary functional assessment

Functional evaluation of coronary vasomotion encompasses the assessment of dynamic changes in coronary lumen, vessel wall, blood flow, intracoronary pressure and myocardial perfusion in response to specific pharmacologic stimuli. These parameters are obtained to characterize mechanisms of physiologic regulation and to evaluate pathophysiologic processes and potential therapeutic strategies, especially with regard to the development of coronary atherosclerosis. To this end, a variety of direct (invasive) and indirect (non-invasive) diagnostic tools are employed. Among the invasive methods are registration of intracoronary Doppler flow, coronary pressure measurements, quantitative coronary angiography and intravascular ultrasound. The non-invasive modalities consist of coronary Doppler echocardiography, positron emission tomography, myocardial scintigraphy and magnetic resonance imaging. Because of the different technical and physiological principles involved, these methods are complementary by providing independent access to different aspects. The combined invasive functional testing as employed in the cardiac catheterization laboratory allows for a simultaneous synopsis of high-resolution coronary imaging and direct measurement of physiologic parameters during local application of defined pharmacologically active substances. However, the demands in terms of equipment, time and operator skills are high and limit this combined invasive approach to specialized centers. Besides these research purposes, a number of functional methods has entered the clinical arena. They are employed to evaluate the hemodynamic significance of coronary lesions and to assess functional outcome of therapeutic interventions in the catheterization laboratory. The underlying principles and applications of the different methods are described and an overview of selected results is presented.     

Atherosclerosis: imaging techniques and the evolving role of nuclear medicine

Quantitative assessment of atherosclerotic or atherothrombotic disease during its natural history and following therapeutic interventions is important for understanding the progression and stabilization of the disease and for selecting appropriate medical or surgical interventions. A number of invasive and noninvasive imaging techniques are available to detect and display different characteristics of vascular lesions of clinical and/or research interest. METHODS: Angiography, the traditional "gold standard," detects advanced lesions and measures the degree of stenosis. Angioscopy clearly identifies thrombus. In carotid arteries and arteries in lower extremities, duplex ultrasonography is useful for providing the degree of stenosis, as well as plaque morphology, and assessing changes in wall thickness. RESULTS: Magnetic resonance angiography, being noninvasive, may replace conventional angiography for anatomical imaging of the vasculature. Ultrafast electron beam CT measures the calcium content in the atherosclerotic lesions. Intravascular ultrasound is the only technique that appears to be clinically useful in imaging the unstable, vulnerable plaques in coronary arteries. Magnetic resonance imaging techniques may be able to image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus associated with the plaques. In regard to the nuclear scientigraphic imaging techniques, radiolabeled lipoproteins, platelets and immunoglobulins have shown some clinical potential as imaging agents, but due to poor target-to-background and target-to-blood ratios these agents are not ideal for imaging coronary or even carotid lesions. Technetium-99m-labeled peptides and monoclonal antibody fragments that clear from circulation rapidly and bind specifically to different components of the atherosclerotic lesion showed significant potential in animal models and in limited clinical studies. FRE Peptides capable of binding to GPIIb/IIIA receptors on activated platelets appear to offer significant diagnostic potential for imaging intra-arterial thrombus. Positron emission tomography with metabolic tracers like [18F]-fluorodeoxyglucose (FDG) also appears to offer new opportunities for noninvasive imaging of atherosclerosis and atherothrombosis.     

Whither paediatric dentistry?

The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.