Kevin Wei

Quantification of Myocardial Blood Flow With Ultrasound-Induced Destruction of Microbubbles Administered as a Constant Venous Infusion

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.

Focused Cardiac Ultrasound in the Emergent Setting: A Consensus Statement of the American Society of Echocardiography and American College of Emergency Physicians

The use of ultrasound has developed over the last 50 years into an indispensable first-line test for the cardiac evaluation of symptomatic patients. The technologic miniaturization and improvement in transducer technology, as well as the implementation of educational curriculum changes in residency training programs and specialty practice, have facilitated the integration of focused cardiac ultrasound into practice by specialties such as emergency medicine. In the emergency department, focused cardiac ultrasound has become a fundamental tool to expedite the diagnostic evaluation of the patient at the bedside and to initiate emergent treatment and triage decisions by the emergency physician.

American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography

UNLABELLED ACCREDITATION STATEMENT: The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASE designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit.trade mark Physicians should only claim credit commensurate with the extent of their participation in the activity. The American Registry of Diagnostic Medical Sonographers and Cardiovascular Credentialing International recognize the ASEs certificates and have agreed to honor the credit hours toward their registry requirements for sonographers. The ASE is committed to resolving all conflict-of-interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated. TARGET AUDIENCE This activity is designed for all cardiovascular physicians, cardiac sonographers, and nurses with a primary interest and knowledge base in the field of echocardiography; in addition, residents, researchers, clinicians, sonographers, and other medical professionals having a specific interest in contrast echocardiography may be included. OBJECTIVES Upon completing this activity, participants will be able to: 1. Demonstrate an increased knowledge of the applications for contrast echocardiography and their impact on cardiac diagnosis. 2. Differentiate the available ultrasound contrast agents and ultrasound equipment imaging features to optimize their use. 3. Recognize the indications, benefits, and safety of ultrasound contrast agents, acknowledging the recent labeling changes by the US Food and Drug Administration (FDA) regarding contrast agent use and safety information. 4. Identify specific patient populations that represent potential candidates for the use of contrast agents, to enable cost-effective clinical diagnosis. 5. Incorporate effective teamwork strategies for the implementation of contrast agents in the echocardiography laboratory and establish guidelines for contrast use. 6. Use contrast enhancement for endocardial border delineation and left ventricular opacification in rest and stress echocardiography and unique patient care environments in which echocardiographic image acquisition is frequently challenging, including intensive care units (ICUs) and emergency departments. 7. Effectively use contrast echocardiography for the diagnosis of intracardiac and extracardiac abnormalities, including the identification of complications of acute myocardial infarction. 8. Assess the common pitfalls in contrast imaging and use stepwise, guideline-based contrast equipment setup and contrast agent administration techniques to optimize image acquisition.

Interactions between microbubbles and ultrasound: In vitro and in vivo observations

OBJECTIVES We attempted to examine the interactions between ultrasound and microbubbles. BACKGROUND The interactions between microbubbles and ultrasound are poorly understood. We hypothesized that 1) ultrasound destroys microbubbles, and 2) this destruction can be minimized by limiting the exposure of microbubbles to ultrasound. METHODS We performed in vitro and in vivo experiments in which microbubbles were insonated at different frequencies, transmission powers and pulsing intervals. Video intensity decay was measured in vitro and confirmed by measurements of microbubble size and concentrations. Peak video intensity and mean microbubble myocardial transit rates were measured in vivo. RESULTS Imaging at lower frequencies and higher transmission powers resulted in more rapid video intensity decay (p = 0.01), and decreasing exposure of microbubbles to ultrasound minimized their destruction in vitro. Although these effects were also noted in vivo with venous injections of microbubbles, they were not seen with aortic root or direct coronary artery injections. CONCLUSIONS Ultrasound results in microbubble destruction that is more evident at lower frequencies and higher acoustic powers. Reducing the exposure of microbubbles to ultrasound minimizes their destruction. This effect is most marked in vivo with venous rather than aortic or direct coronary injections of microbubbles. These findings could lead to effective strategies for myocardial perfusion imaging with venous injections of microbubbles.

Noninvasive quantification of coronary blood flow reserve in humans using myocardial contrast echocardiography

Background—We hypothesized that coronary blood flow (CBF) reserve could be quantified noninvasively in humans using myocardial contrast echocardiography (MCE). Methods and Results—Eleven patients with normal epicardial coronary arteries (group I) and 19 with single-vessel coronary stenosis (group II) underwent quantitative coronary angiography, MCE, and CBF velocity measurements at rest and during intravenous adenosine infusion. In group I patients, MCE-derived myocardial blood flow (MBF) velocity reserve (2.4±0.08) was similar to CBF velocity reserve using a Doppler flow wire (2.4±1.1). Patients with a single risk factor had a significantly higher MBF reserve (3.0±0.89) than those with ≥2 risk factors (1.7±0.22). In group II patients, significant differences were found in MBF velocity reserve in patients with mild (<50%), moderate (50% to 75%), or severe (>75%) stenoses (2.2±0.40, 1.6±0.65, and 0.55±0.19, respectively;P =0.005). A linear relation was found between flow velocity reserve determined using the 2 methods (r =0.76, P <0.001), and a curvilinear relation was noted between the percent coronary stenosis measured using quantitative coronary angiography and velocity reserve using both methods. Conclusions—CBF reserve can be measured in humans using MCE. This method may allow the noninvasive assessment of coronary stenosis severity and the detection of microvascular dysfunction.

Quantification of renal blood flow with contrast-enhanced ultrasound

OBJECTIVES The goal of this study was to determine the ability of contrast-enhanced ultrasound (CEU) to quantify renal tissue perfusion. BACKGROUND The kinetics of tracers used to assess renal perfusion are often complicated by countercurrent exchange, tubular transport or glomerular filtration. We hypothesized that, because gas-filled microbubbles are pure intravascular tracers with a rheology similar to that of red blood cells, CEU could be used to quantify renal tissue perfusion. METHODS During a continuous venous infusion of microbubbles (SonoVue), regional renal perfusion was quantified in nine dogs using CEU by destroying microbubbles and measuring their tissue replenishment with intermittent harmonic imaging. Both renal blood volume fraction and microbubble velocity were derived from pulsing-interval versus video-intensity plots. The product of the two was used to calculate renal nutrient blood flow. Renal arterial blood flow was independently measured with ultrasonic flow probes placed directly on the renal artery and was increased using dopamine and decreased by placement of a renal artery stenosis. RESULTS An excellent correlation was found between cortical nutrient blood flow using microbubbles and ultrasonic flow probe-derived renal blood flow (r = 0.82, p < 0.001) over a wide range (2.5 fold) of flows. CONCLUSIONS Ultrasound examination during microbubble infusion can be used to quantify total organ as well as regional nutrient blood flow to the kidney.

Basis for detection of stenosis using venous administration of microbubbles during myocardial contrast echocardiography: bolus or continuous infusion?

OBJECTIVES This study sought to determine the basis of detection of stenosis by myocardial contrast echocardiography using venous administration of microbubbles and to define the relative merits of bolus injection versus continuous infusion. BACKGROUND The degree of video intensity (VI) disparity in myocardial beds supplied by stenosed and normal coronary arteries can be used to quantify stenosis severity after venous administration of microbubbles. However, the comparative merits of administering microbubbles as a bolus injection or continuous infusion has not been studied. METHODS Coronary stenoses of varying severity were created in either the left anterior descending or the left circumflex coronary artery in 18 dogs. Imagent US (AF0150) was given as a bolus injection in 10 dogs (Group I) and as both a bolus injection and a continuous infusion in 8 dogs (Group II). For bolus injections, peak VI was derived from time-intensity plots. During continuous infusion, microbubble velocity and microvascular cross-sectional area were derived from pulsing interval versus VI plots. Myocardial blood flow (MBF) was determined using radiolabeled microspheres. RESULTS During hyperemia, VI ratios from the stenosed versus normal beds correlated with radiolabeled microsphere-derived MBF ratios from those beds for both bolus injections (r = 0.81) and continuous infusion (r = 0.79). The basis for detection of stenosis common to both techniques was the decrease in myocardial blood volume distal to the stenosis during hyperemia. The advantage of continuous infusion over bolus injection was the abolition of posterior wall attenuation and the ability to quantify MBF. CONCLUSIONS Both bolus injection and continuous infusion provide quantitative assessment of relative stenosis severity. Compared with bolus injection, continuous infusion also allows quantification of MBF and data acquisition without attenuation of any myocardial bed.

Myocardial contrast echocardiography.

“An untroubled mind, no longer seeking to consider what is right and what is wrong; A mind beyond judgements, watches and understands.” The Buddha (translated from the Dhammapada ) The purpose of this article is to describe our personal experience in translating observations made in the experimental laboratory using MCE into the clinical setting. It is not intended to be an exhaustive review of MCE, for which readers are referred elsewhere.1 2 3 The work of others in MCE and related subjects will be mentioned only when it has influenced our own work. Our bench-to-bedside experience with MCE over the past 15 years will be discussed under these six broad categories: (a) technical issues; (b) AMI, (c) detection of CAD, (d) applications in the operating room, (e) quantification of myocardial perfusion, and (f) work in progress. Historically, it has not been possible to directly assess myocardial perfusion with echocardiography. Its clinical focus has involved the evaluation of cardiac chamber size and function, valve morphology and kinetics, pericardial space and great vessels, and intracavitary blood flow velocities. Yet, echocardiography is highly suited for the evaluation of myocardial perfusion for the following reasons: (a) It has very good spatial resolution (<1 mm in the axial direction), which is far superior to that offered by SPECT and positron emission tomography, although not as good as magnetic resonance imaging and ultrafast cine computed tomography; (b) its temporal resolution is excellent (30 to 120 Hz) and exceeds that of other commonly used imaging technologies; (c) for an imaging modality, it is inexpensive and has low overhead costs; (d) it is an integral tool in the day-to-day activities of clinical cardiologists, who can obtain advanced training in its use without needing to learn an entirely new technology. The study of myocardial perfusion with echocardiography involves …

Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography

To define the role of capillaries in the control of coronary blood flow (CBF) reserve, we developed a model of the coronary circulation and evaluated experimental data in its context. Our model comprised three compartments connected in series (arterial, capillary, and venous), each with its own resistance. The resistance in each vascular compartment was derived from the model based on hemodynamic data obtained in nine dogs during baseline and stenosis, both at rest and during hyperemia. The capillary hydrostatic pressure was assumed to be constant in all stages. Although in the absence of stenosis, the contribution of capillaries to total myocardial vascular resistance was only 25 +/- 5% at rest, it increased to 75 +/- 14% during hyperemia, despite the total myocardial vascular resistance decreasing by 51 +/- 13%. In the presence of a noncritical stenosis, total myocardial vascular resistance decreased by 22 +/- 10% at rest, with no change in capillary resistance. During hyperemia, total myocardial vascular resistance increased by 58 +/- 50% in the presence of the noncritical stenosis. In this situation, because arteriolar and venular resistances were already minimal, the increase in myocardial vascular resistance was due to increased capillary resistance, making it the predominant source (84 +/- 8%) of total myocardial vascular resistance. Myocardial video intensity (VI) on myocardial contrast echocardiography (MCE), which reflects capillary blood volume, decreased distal to the stenosis during hyperemia. In the presence of a flow-limiting stenosis at rest, myocardial VI also decreased, indicating that decrease in CBF was associated with an increase in capillary resistance. Our findings also provide an alternative explanation for the critical coronary closing pressure. Thus, contrary to previously held notions, capillaries play a vital role in the regulation of CBF.

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.