(Circulation. 2001;103:2560.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Noninvasive Quantification of Coronary Blood Flow Reserve in Humans Using Myocardial Contrast Echocardiography
Presented at the Samuel Levine Young Investigator Award Competition of the Council on Clinical Cardiology at the 73rd Annual Scientific Sessions of the American Heart Association, November 12–15, 2000, New Orleans, La, and published in abstract form (Circulation. 2000;102[suppl II]:II-H).
From the Cardiac Imaging Center and the Cardiovascular Division, University of Virginia School of Medicine, Charlottesville, Va.
Correspondence to Kevin Wei, MD, Cardiovascular Division, Box 158, Medical Center, University of Virginia, Charlottesville, VA 22908. E-mail kw6n{at}virginia.edu
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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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.
Key Words: blood flow • coronary disease • contrast media • echocardiography
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Because the microvascular rheology of the microbubbles used for myocardial contrast echocardiography (MCE) is similar to that of red blood cells,1 2 MCE has been shown to noninvasively and accurately quantify myocardial blood flow (MBF) velocity.3 In this study, we hypothesized that MCE could also be used to determine coronary blood flow (CBF) velocity reserve noninvasively in humans by measuring microbubble (or red blood cell) velocity at rest and during maximal hyperemia. This hypothesis was tested in patients undergoing cardiac catheterization. MCE data were compared with CBF velocity measurements using an intracoronary Doppler flow wire, and both sets of data were compared with percent luminal diameter stenosis from quantitative coronary angiography (QCA).
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Patient Population
The study protocol was approved by the Human Investigation Committee at the University of Virginia. A total of 30 patients >18 years of age who were scheduled for elective coronary angiography were enrolled in the study. Group I patients (n=11) had angiographically normal coronary arteries, and group II patients (n=19) had a noncritical coronary stenosis in a single vascular territory. Patients were also screened to evaluate their echocardiographic image quality. Those in whom both the endocardial and epicardial borders in the coronary artery territory of interest could not be visualized were not recruited. All patients gave written, informed consent to participate in the study.
Myocardial Contrast
Echocardiography
Intermittent harmonic imaging was performed with a
phased-array system interfaced to a S3 transducer that transmits
ultrasound at a mean frequency of 1.3 MHz and receives it at a mean
frequency of 3.6 MHz. The transmit power was set at maximum, and
compression was set at 50 dB. Gain settings were optimized at the
beginning of each study and subsequently held constant. Imaging was
performed using either the apical 4-, 2- or 3-chamber views, depending
on the perfusion territory of interest, which was based on the
angiographic results. The pulsing interval (PI) was gated to the ECG
and progressively increased from 80 ms to 10 s. Up to 8 images,
acquired at each PI, were recorded on 1.25-cm S-VHS videotape
(Panasonic AG-MD830, Matsushita Electric Corp).
MCE was performed using a continuous infusion of
Definity.3
A dose of 0.04 mL/kg was diluted in 100 mL of normal saline and
infused intravenously at a rate of 120 to 180 mL/h. The
adequacy of myocardial opacification was confirmed by imaging at every
fifth cardiac cycle, and the infusion rate was individually adjusted in
each patient to produce adequate myocardial opacification with minimal
left atrial shadowing. Absence of any change in myocardial video
intensity (VI) over 3 successive frames by visual assessment
indicated that steady state had been reached (
2 minutes after
starting the
infusion).3
Data were transferred from videotape to an off-line computer for analysis.3 At least 5 images acquired at baseline (precontrast) and at each PI were manually aligned. Only images in the same location within the ultrasound sector and with a similar orientation were selected. Those that were either shifted due to breathing or were off-axis due to changes in transducer position or patient movement were not selected for alignment. Large regions of interest were placed over the mid-myocardium, and VI was automatically measured from these regions from each of the aligned images. PI versus background-subtracted VI plots were then generated, and they were fitted to the exponential function y=A(1-e-ßt), where y is the VI at a PI of t, A is the plateau where VI represents myocardial blood volume, and ß represents the mean microbubble velocity.3
In addition to the above analyses, color-coding was
applied to background-subtracted images to visually enhance regional
differences in myocardial contrast
enhancement.3 All pixels with
a gray-scale value >10 were assigned a color based on the degree of
contrast enhancement, where shades of red, progressing to hues of
orange, yellow, and white represent incremental contrast
opacification. Pixels with gray-scale values 
10 were
considered to represent noise and were not assigned a color.
The left ventricular cavity was masked
out.
QCA and Determination of CBF Velocity
All QCA and Doppler flow wire measurements were
performed by a single experienced operator (M.R.) who has performed
>100 of each of these procedures. A 0.014-inch intracoronary
Doppler flow wire (FloWire, Cardiometrics)
was placed in the vessel of
interest.4 In group I
patients, the wire was placed in a nonbranching portion of the mid-left
anterior descending (LAD) coronary artery. Care was taken to
position the tip of the wire in the middle of the lumen, as coaxial as
possible with the walls of the vessel, and in a location that gave the
best spectral Doppler signal. The position of the tip of the flow
wire was documented by cineangiography. The average peak velocity was
automatically determined by integration of the spectral Doppler
signal.5 In group II
patients, spectral Doppler signals were continuously recorded
as the flow wire was advanced into the coronary artery.
Baseline flow velocities proximal to the stenosis were first
determined. As the wire was advanced across the lesion, flow velocities
increased, and the wire was continually advanced to a location where
all poststenotic acceleration of flow had ceased (beyond the
vena contracta).
For QCA, digital cineangiographic images acquired in orthogonal projections were used. Calibration was performed using the coronary guiding catheter as a reference (6F=2.0 mm, 7F=2.33 mm, and 8F=2.67 mm), with the image magnified 4x. The coronary artery segment of interest was selected, and the axis and edges of the artery were automatically defined. In group II patients, minimal lumen diameter and percent diameter stenosis were computed in a standard manner using the proximal normal vessel segment as the reference in a single-plane, "worst-view" angulation.4 The automated edge detection methodology was visually inspected to assure that lumen edges were correctly identified.
Protocol
Coronary angiography was first performed to
define the coronary anatomy. CBF velocity and
hemodynamics were acquired, and QCA and MCE were
performed at baseline. An intravenous infusion of 140 µg
· kg–1 ·
min–1 adenosine
(Adenoscan, Fujisawa Healthcare, Deerfield, Ill)
was then initiated to induce maximal coronary
hyperemia. CBF velocity was measured along with other
hemodynamics, and QCA and MCE were repeated. If
high-dose adenosine could not be tolerated by the patient
(because of hypotension, adverse effects, etc), the dose was reduced to
70 µg · kg–1 ·
min–1. CBF velocity and MBF velocity
reserve were calculated by dividing the values obtained during maximal
hyperemia by those obtained at rest.
Statistical Methods
Comparisons between 2 stages were made with unpaired
Student’s t test, and those
between >2 stages were performed with repeated measures ANOVA.
Interstage differences were confirmed using an unpaired Student’s
t test. All correlations were
performed with least-squares fit regression analysis.
Differences were considered significant at
P<0.05
(2-sided).
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Group I Patients
MCE data were not suitable for analysis in one group I patient because of image artifacts, so data from the remaining 10 patients are presented. Their median age was 47 years (range, 37 to 61 years), and 6 patients were men. By design, none of the patients had any coronary artery stenoses. Background-subtracted color-coded images (apical 2-chamber view) from one patient at a short PI from baseline and during adenosine infusion are illustrated in Figure 1
. The corresponding Doppler flow wire velocity
signals from the 2 stages are also shown. The average peak velocity
increased from 28 to 89 cm/s during adenosine infusion. At
baseline, little myocardial contrast enhancement is seen at the short
PI (1.8 s) shown. The increase in CBF velocity during adenosine
resulted in more rapid microbubble replenishment of the myocardial
microcirculation, causing a greater degree of myocardial contrast
enhancement at a PI of 1.5 s compared with baseline.
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The PI versus VI curves obtained at baseline and during
hyperemia from the patient in
Figure 1
are shown in
Figure 2. The microbubble velocity is more rapid during
adenosine infusion than at baseline. In this instance, ß
increased from 0.5 s–1 to 0.9
s–1 during adenosine, which matched
the increase in average peak velocity on Doppler flow wire. The
plateau VI (myocardial blood volume), however, was similar during the 2
stages, because myocardial blood volume did not change in the absence
of any changes in systemic hemodynamics during
adenosine.3
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) and hyperemia (•) are shown. See text for details.
The hemodynamic, Doppler flow wire, and
MCE data acquired at baseline and during adenosine infusion
from all group I patients are shown in
Table 1. The mean dose of adenosine used was 95±35
µg · kg–1 ·
min–1. Doppler flow wire average peak
velocity more than doubled, and the epicardial CBF almost tripled,
resulting in a CBF velocity reserve of almost 2.5 and a CBF reserve of
nearly 3.0.
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In the absence of any changes in systemic
hemodynamics during adenosine, no significant
change in MBV or plateau VI was noted between baseline and
hyperemic stages (26±11 versus 30±8, respectively,
P=0.30). The increase in MBF
during adenosine was therefore met entirely by increases in
microbubble velocity
(Table 1). The microbubble velocity reserve determined using
MCE was identical to CBF velocity reserve determined from Doppler
flow wire. There were 5 group I patients with only a single cardiac
risk factor (2 with hypertension and 3 with
hypercholesterolemia, all of whom were on
medical therapy); the other patients had 2 risk factors. Both the MBF
and CBF velocity reserve were significantly higher in patients with a
single risk factor (3.0±0.89 and 3.7±1.1) than it was in those with
2 risk factors (1.7±0.2,
P=0.01, and 1.6±0.4,
P=0.002).
Group II Patients
MCE images could not be analyzed in 3 group II
patients because of image artifacts, so data from the remaining 16
patients are presented. Their mean age was 56 years (range, 38
to 75 years), and 12 patients were men. Color-coded images of an apical
2-chamber view from a patient with a moderate LAD stenosis
(60% by QCA) obtained at rest and during hyperemia are
illustrated in
Figure 3. The corresponding PI versus VI curves from the LAD
and left circumflex beds are also shown. Because the stenosis
was not flow-limiting at rest, the change in VI at different PIs is
similar in both beds at baseline, resulting in a similar microbubble
velocity. During hyperemia induced with 140 µg ·
kg–1 · min–1
adenosine, the increase in CBF velocity was less in the
stenosed LAD compared with the left circumflex bed, resulting in lower
microbubble velocities in the former. Therefore, at a short PI of
2 s, perfusion mismatch is noted on the MCE image. In this
instance, peak VI was lower in the LAD bed, even at longer
PIs.
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The hemodynamic, Doppler flow wire, and
MCE data acquired at rest and during adenosine infusion from
all group II patients are depicted in
Table 2. Stenoses in individual patients were
divided into mild (<50%), moderate (50% to 75%), and severe
(>75%) on the basis of QCA. No changes in heart rate or blood
pressure were noted between rest and adenosine stages in any
patient. None of the stenoses was critical in severity, so
resting Doppler flow wire average peak velocities were similar
between all patients. In contradistinction, during adenosine
infusion, these values were significantly different between the 3
groups
(Table 2).
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Similar to the flow wire data, no significant difference was
found in the absolute values of MCE-determined MBF velocity at rest for
patients with mild, moderate, or severe stenosis
(Table 2). Although absolute MBF velocity was not
significantly different between the 3 groups during adenosine
infusion, MBF velocity reserve was again significantly different
between them
(Table 2). Myocardial blood volume was similar between the 3
groups at rest (51±16, 52±18, and 56±0.10 for mild, moderate, and
severe stenoses, respectively;
P=0.94) and during
hyperemia (48±15, 54±24, and 40±23 for mild, moderate, and
severe stenoses, respectively;
P=0.66).
ß Reserve and CBF Velocity Reserve Versus
Coronary Stenosis Severity
A linear correlation (y=0.6x+1) was noted
between Doppler flow wire (x) and MCE-derived ß reserves (y) from
all patients (r=0.78,
P<0.001, SEE=0.55).
Figure 4 illustrates the relation between percent luminal
diameter narrowing derived using QCA versus Doppler flow wire
average peak velocity and MCE-derived MBF velocity reserve in group II
patients. Both relations show a fit to the function
y=A(1-eß(x–xo)), but the fit
for MCE-derived velocity is better. A failure of MBF velocity to
increase >1.5 times that at baseline indicates the presence of >70%
coronary artery
stenosis.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Measuring CBF Reserve with MCE
In this study, we showed for the first time that CBF reserve can be measured noninvasively in humans using MCE. We also showed that increases in microbubble (or red blood cell) velocity occur in parallel with increases in CBF induced by the administration of adenosine. Consequently, the ratio of hyperemic and resting MBF velocities measured with MCE correlates very well with CBF reserve.
Using a canine experimental model, we previously showed that during hyperemia, when coronary arterioles and venules are fully dilated, the resistance to CBF is mediated largely through capillaries,6 which lack smooth muscle and do not change their size with a coronary vasodilator. When hyperemia is induced in the presence of a stenosis, myocardial vascular resistance distal to a stenosis increases, despite maximal dilatation of the coronary arterioles and venules.6 7 This increase in resistance is caused by a decrease in capillary blood volume distal to a stenosis, resulting in a reversible perfusion defect during myocardial perfusion imaging. We also showed that the magnitude of a perfusion defect during hyperemia is directly related to the severity of the stenosis.6 7 Thus, measuring plateau myocardial VI before and after the infusion of a coronary vasodilator also provides an assessment of the severity of coronary stenosis.
Although this method is accurate for the assessment of coronary stenosis severity in open-chest canine models, it has drawbacks in the clinical setting. First, the blood concentration of microbubbles must be the same during rest and hyperemia, which is not always feasible, even with a continuous infusion. We previously showed that although plateau VI was affected by small changes in the blood concentration of microbubbles, microbubble velocity was not similarly affected.3 Second, because the ultrasound backscatter within a myocardial region has to be compared between rest and stress stages, the imaging plane has to be identical for both examinations. Although this is possible in animal preparations, where the ultrasound transducer is held in a fixed position, it is difficult in patients. Third, the acoustic energy within the ultrasound field is heterogenous, with less energy at the margins and at greater imaging depths.8 Consequently, the backscatter from microbubbles is also inhomogeneous. Attenuation-induced and other artifacts are also likely to cause a spurious decrease in backscatter. Although absolute backscatter estimates may be erroneous as a result of these factors, the rate of change of backscatter with increasing PIs is not affected. Finally, because myocardial blood volume does not change with adenosine in the absence of coronary stenosis,3 CBF reserve cannot be determined from measurements of plateau VI alone. Thus, as shown from the results of the current study, measuring changes in MBF velocity rather than plateau VI provides a more robust and accurate estimate of CBF reserve with MCE in the clinical setting.
CBF reserve measurements in the catheterization laboratory require expertise in both the Doppler flow wire technique and QCA. Proper use of the Doppler flow wire requires careful positioning of the wire tip in a fairly straight segment of the artery away from side branches. Highly tortuous and distal segments are difficult to assess with this technique. It is also necessary for the operator to recognize an acceptable Doppler signal and to interpret the data correctly both at baseline and under maximal hyperemia. QCA requires technical expertise as well. The lesion must be well opacified to allow accurate edge delineation, and the arterial segment must lie in the same plane as the catheter tip to allow proper calibration. The presence of inexperienced operators with either of these techniques might lead to inaccurate measurement of CBF reserve.
An interesting finding of our study is the curvilinear
relation between MCE-determined MBF velocity reserve and percent
coronary artery stenosis determined using QCA. This
relation is more similar to that reported by Gould and
Lipscomb9 than the relation
between Doppler flow wire–determined CBF velocity reserve versus
coronary stenosis
(Figure 4). It is likely that in the latter situation, CBF
velocity measurements were more prone to error from the angle
dependence of Doppler than the measurement of tissue MBF velocity
using MCE.
Limitations
Maximal doses of adenosine could not be used in
all patients because of side effects. A higher dose of
adenosine may have allowed greater increases in
hyperemic CBF, which could potentially have permitted better
separation of the degrees of stenosis and allowed the detection
of milder stenoses. As would be expected, MBF and CBF velocity
reserves of group I patients who had 2 risk factors were low in our
study. Although these patients had normal coronary arteries on
angiography, they were not evaluated by intravascular ultrasound or for
the presence of microvascular disease. Our values of MBF velocity
reserve, therefore, reflect the combined effects of both the epicardial
coronary stenosis and microvascular dysfunction on flow
reserve. Because the prevalence of these conditions was similar in our
patients with different degrees of coronary stenosis,
our data indicate that an abnormal MBF velocity reserve can still be
used to detect physiologically significant
stenoses.
The addition of subjects with a low probability of coronary artery disease would have been useful because they would most likely have shown an even higher reserve. The ability of MCE to measure high flows still needs to be demonstrated in humans, although it has clearly been shown in animals.3
Acquisition of MCE data are currently tedious and time-consuming. Image alignment, background subtraction, and selection of proper regions of interest require sufficient expertise and custom-designed software. Newer imaging methods are being developed that allow microbubble destruction with a high mechanical index followed by data acquisition using a low mechanical index that minimizes bubble destruction.10 Thus, PI versus VI curves can potentially be generated in real-time.
Although some bioeffects have been reported with the use of microbubbles and high-energy ultrasound, these have been noted only in ex vivo models where exposed muscle has been subjected to ultrasound exposure.11 Otherwise, microbubbles have been found to be safe in several thousand patients evaluated in clinical trials. As stated above, newer methods are currently being designed to image microbubbles in vivo using low-energy ultrasound.10
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Acknowledgments |
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Supported in part by grants from the National Institutes of Health, Bethesda, Md (R01-HL48890); the Mid-Atlantic Affiliate of the American Heart Association, Baltimore, Md (B98458V); the Fourjay Foundation, Williamsport, Pa; and DuPont Pharmaceuticals Co, Wilmington, De. Fujisawa Healthcare, Deerfield, Ill, provided Adenoscan, and Agilent Technologies, Andover, Mass, provided an equipment grant. K. Wei is the recipient of a mentored Clinical Scientist Development Award (K08-HL03909), and M. Coggins was the recipient of a Medical Student Research Fellowship from the American Diabetes Association, Alexandria, Va.
Received September 28, 2000; revision received February 22, 2001; accepted March 6, 2001.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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1. Jayaweera AR, Edwards N, Glasheen WP, et al. In-vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography: comparison with radiolabeled red blood cells. Circ Res. 1994;74:1157–1165.
2.
Ismail S, Jayaweera
AR, Camarano G, et al. Relation between air-filled albumin
microbubble and red blood cell rheology in the human
myocardium: influence of echocardiographic
systems and chest wall attenuation.
Circulation. 1996;94:445–451.
3.
Wei K, Jayaweera
AR, Firoozan S, et al. Quantification of myocardial blood flow with
ultrasound induced destruction of microbubbles administered as a
constant venous infusion.
Circulation. 1998;97:473–483.
4. McPherson JA, Robinson PS, Powers ER, et al. Angiographic findings in patients undergoing catheterization for recurrent symptoms within 30 days of successful coronary intervention. Am J Cardiol. 1999;84:589–592.[Medline] [Order article via Infotrieve]
5. Ragosta M, Powers ER, Samady H, et al. Relation between the extent of residual myocardial viability and coronary flow reserve in patients with recent myocardial infarction. Am Heart J. In press.
6.
Jayaweera AR, Wei
K, Coggins M, et al. Role of capillaries in determining
coronary blood flow reserve: new insights using myocardial
contrast echocardiography.
Am J Physiol. 1999;277:H2363–H2372.
7.
Wei K, Jayaweera
AR, Firoozan S, et al. The basis for stenosis detection using
venous administration of microbubbles during myocardial contrast
echocardiography: bolus or continuous infusion?
J Am Coll Cardiol. 1998;32:252–260.
8. Senior R, Kaul S, Soman P, et al. Power-Doppler contrast echocardiography: a new technique for assessing myocardial perfusion. Am Heart J. 2000;139:245–251.[Medline] [Order article via Infotrieve]
9. Gould KL, Lipscomb K. Effects on coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974;34:48–55.[Medline] [Order article via Infotrieve]
10. Simpson DH, Burns P. Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents. IEEE Ultrason Symp. 1997;1597–1600.
11.
Skyba DM, Price
RJ, Linka AZ, et al. Direct in vivo visualization of microvessel
rupture and tissue injury caused by intravascular destruction of
microbubbles by ultrasound.
Circulation. 1998;98:290–293.
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 R. Scognamiglio, C. Negut, S. V. de Kreutzenberg, A. Tiengo, and A. Avogaro Effects of Different Insulin Regimes on Postprandial Myocardial Perfusion Defects in Type 2 Diabetic Patients Diabetes Care, January 1, 2006; 29(1): 95 - 100. [Abstract] [Full Text] [PDF]
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R. Scognamiglio, C. Negut, A. Ramondo, A. Tiengo, and A. Avogaro Detection of Coronary Artery Disease in Asymptomatic Patients With Type 2 Diabetes Mellitus J. Am. Coll. Cardiol., December 13, 2005; (2005) j.jacc.2005.10.008v1. [Abstract] [Full Text] [PDF]
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 D. L. Miller, P. Li, C. Dou, D. Gordon, C. A. Edwards, and W. F. Armstrong Influence of Contrast Agent Dose and Ultrasound Exposure on Cardiomyocyte Injury Induced by Myocardial Contrast Echocardiography in Rats Radiology, October 1, 2005; 237(1): 137 - 143. [Abstract] [Full Text] [PDF]
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R. Senior, R. Janardhanan, P. Jeetley, and L. Burden Myocardial Contrast Echocardiography for Distinguishing Ischemic From Nonischemic First-Onset Acute Heart Failure: Insights Into the Mechanism of Acute Heart Failure Circulation, September 13, 2005; 112(11): 1587 - 1593. [Abstract] [Full Text] [PDF]
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K. Wei, K. L. Tong, T. Belcik, P. Rafter, M. Ragosta, X.-Q. Wang, and S. Kaul Detection of Coronary Stenoses at Rest With Myocardial Contrast Echocardiography Circulation, August 23, 2005; 112(8): 1154 - 1160. [Abstract] [Full Text] [PDF]
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R. Scognamiglio, C. Negut, S. V. De Kreutzenberg, A. Tiengo, and A. Avogaro Postprandial Myocardial Perfusion in Healthy Subjects and in Type 2 Diabetic Patients Circulation, July 12, 2005; 112(2): 179 - 184. [Abstract] [Full Text] [PDF]
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R. Vogel, A. Indermuhle, J. Reinhardt, P. Meier, P. T. Siegrist, M. Namdar, P. A. Kaufmann, and C. Seiler The quantification of absolute myocardial perfusion in humans by contrast echocardiography: Algorithm and validation J. Am. Coll. Cardiol., March 1, 2005; 45(5): 754 - 762. [Abstract] [Full Text] [PDF]
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P. MacCarthy, A. Berger, G. Manoharan, J. Bartunek, E. Barbato, W. Wijns, G. R. Heyndrickx, N. H.J. Pijls, and B. De Bruyne Pressure-derived measurement of coronary flow reserve J. Am. Coll. Cardiol., January 18, 2005; 45(2): 216 - 220. [Abstract] [Full Text] [PDF]
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A Hagendorff, A Werner, D Pfeiffer, and H Becher Estimation of vasodilator response by analysis of Doppler intensity kinetics with myocardial contrast echocardiography using an intravenous standardized bolus administration Eur J Echocardiogr, August 1, 2004; 5(4): 272 - 283. [Abstract] [Full Text] [PDF]
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S. B. Feinstein The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H450 - H457. [Abstract] [Full Text] [PDF]
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M. Peltier, D. Vancraeynest, A. Pasquet, T. Ay, V. Roelants, A.-M. D'hondt, J. A. Melin, and J.-L. J. Vanoverschelde Assessment of the physiologic significance of coronary disease with dipyridamole real-time myocardial contrast echocardiography: Comparison with technetium-99m sestamibi single-photon emission computed tomography and quantitative coronary angiography J. Am. Coll. Cardiol., January 21, 2004; 43(2): 257 - 264. [Abstract] [Full Text] [PDF]
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Y. Takagi, K. Ohmori, K. Yukiiri, I. Kondo, Y. Yu, A. Oshita, H. Takeuchi, K. Mizushige, and M. Kohno Quantitative assessment of coronary stenosis by harmonic power Doppler with a simple pulsing sequence and vasodilator stress in patients J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2060 - 2067. [Abstract] [Full Text] [PDF]
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T Muro, T Hozumi, H Watanabe, H Yamagishi, M Yoshiyama, K Takeuchi, and J Yoshikawa Assessment of myocardial perfusion abnormalities by intravenous myocardial contrast echocardiography with harmonic power Doppler imaging: comparison with positron emission tomography Heart, February 1, 2003; 89(2): 145 - 149. [Abstract] [Full Text] [PDF]
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S Fukuda, T Muro, T Hozumi, H Watanabe, K Shimada, M Yoshiyama, K Takeuchi, and J Yoshikawa Changes in transmural distribution of myocardial perfusion assessed by quantitative intravenous myocardial contrast echocardiography in humans Heart, October 1, 2002; 88(4): 368 - 372. [Abstract] [Full Text] [PDF]
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 A. Hansen, B.-L. Johansson, J. Wahren, and H. von Bibra C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes Diabetes, October 1, 2002; 51(10): 3077 - 3082. [Abstract] [Full Text] [PDF]
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