From the Cardiovascular Division, University of Virginia School of
Medicine (Charlottesville).
Correspondence to Sanjiv Kaul, MD, Cardiovascular Division, Medical Center, Box 158, University of Virginia, Charlottesville, VA 22908. E-mail sk{at}virginia.edu
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-ßt),
where A is the plateau video intensity reflecting the
microvascular cross-sectional area, and ß reflects the rate of rise
of video intensity and, hence, microbubble velocity. Excellent
correlations were found between flow and ß, as well as flow and the
product of A and ß.
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.
A number of recent advances have made myocardial opacification possible
through a venous injection of microbubbles. Air-filled microbubbles
rapidly decrease in size in the circulation because the highly
diffusible oxygen and nitrogen leak out of the bubbles and, being
soluble, dissolve in blood. Because the backscatter of a bubble is
related to the sixth power of its radius,3 even a
small decrease in size causes a large decrease in backscatter.
Myocardial opacification is therefore not seen when air-filled bubbles
are injected intravenously. This limitation has been
overcome with the development of "second-generation" bubbles that
contain high-molecular-weight gases that are nondiffusible and less
soluble. These bubbles do not change their size appreciably after
entering the systemic circulation and thus retain their backscattering
properties. Their venous administration has been shown to result in
successful myocardial opacification.4 5 6 7 8
We have recently shown that exposure of microbubbles to ultrasound
results in their destruction.9 This effect could
be related to the induction of nonlinear oscillations in
the microbubbles or represent a nonspecific effect related to
the acoustic power. Regardless of the exact mechanism of
ultrasound-induced microbubble destruction, the acoustic emissions from
oscillating or imploding microbubbles contain harmonics of the
frequency to which the bubbles were initially
exposed.10 11 Because harmonic signals emanate
mostly from bubbles rather than tissue, selective reception of these
signals results in an increased signal-to-noise
ratio.4 5 9 12
For this study, we hypothesized that ultrasound-induced destruction of
intravenously delivered bubbles can be used to quantify
myocardial perfusion. If microbubbles are administered as a continuous
infusion, then their destruction within the myocardium and
measurement of their reappearance rate will provide a measure of mean
myocardial microbubble velocity. Furthermore, the microbubble
concentration in the myocardium during steady state will
reflect the sum of the myocardial microvascular CSA. Knowing both the
mean myocardial microbubble velocity and the myocardial microvascular
CSA can then provide a measure of MBF. We tested these hypotheses in ex
vivo, in vitro, and in vivo experiments.
Because VI is proportional to the effective microbubble concentration
within the beam thickness at any PI (when the relation between the two
is linear13 ), it will be proportional to
d/E. Substituting for d, from equation 1
The model predicts a sharp demarcation between the upslope and plateau
phases of the PI-VI relation (Fig 2A
Because the slope of the tangent to the curves is given by
dv/dt=AßE-ßt,
the slope at the origin (t=0) is Aß. As shown
in Fig 2A
Strategies to Test the Model
Contrast Echocardiography
The ultrasound transducer was fixed in position with a custom-designed
clamp. The transmit power was set at 75% of maximum. The peak negative
acoustic pressure at the focal point was 1.1 MPa, and the mechanical
index was 0.7. The image depth and transmit focus were each set at 8
cm, and a maximal compression of 60 dB was used. No time-gain or
lateral-gain compensation was used. Data were recorded on 1.25-cm
videotape with a S-VHS recorder (Panasonic AG-MD830;
Matsushita).
Contrast Agent
Hemodynamic Measurements
Flow Measurements
Nutrient Flow
At the end of the experiment, the short-axis slice of the LV
corresponding to the echocardiographic image was cut
into 16 wedge-shaped pieces, excluding the papillary muscles. Each
piece was further divided into epicardial, mid-myocardial, and
endocardial segments. The tissue and reference blood samples were
counted in a well counter with a multichannel analyzer (model
1282; LKB Wallac), using corrections for activity spilling between
energy windows.
MBF to each epicardial, mid-myocardial, and endocardial segment was
calculated from the equation
Qm=(Cm ·
Qr)/Cr, where
Qm is MBF (mL ·
min-1), Cm is tissue
counts, Qr is rate of arterial sample
withdrawal (mL · min-1), and
Cr is arterial reference sample
counts.13 Transmural MBF (mL ·
min-1 · g-1) to
each of the 16 wedge-shaped pieces was calculated as the quotient of
the summed flows to the individual segments within that piece and their
combined weight. The perfusion bed of either the LAD or LCx was
determined using intracoronary injections of Albunex (Molecular
Biosystems).1 2 Mean MBF to each perfusion bed
was then calculated by averaging the transmural MBF in the central 50%
to 75% of the pieces in each bed.
Experimental Preparations and Protocols
In the first experiment, the beaker contained 0.5 mL of MRX-115 in 3 L
of 0.9% saline, and the flow rate was held constant in both veins at
52 mL · min-1 (flow velocity=1.7 cm
· s-1). Samples of the solutions were
withdrawn from the tubing just proximal and distal to the transducer
location and immediately placed on a hemacytometer; the number of
microbubbles were counted using light microscopy (magnification x40).
In the control stage, no ultrasound was transmitted, whereas in the
test stages, it was transmitted using various PI.
In the second experiment, the beaker contained 0.01 mL of MRX-115 in
560 mL of 0.9% saline, which resulted in adequate opacification in the
veins without system saturation or attenuation. The flow in one vein
was held constant at 52 mL · min-1,
whereas that in the other vein was increased from 52 to 200 mL ·
min-1 in random order, which corresponds to flow
velocities ranging from 1.7 to 6.7 cm ·
s-1. Imaging was performed at PI of 33 and 200
ms.
In Vitro Experiments
A solution of 0.2 mL of MRX-115 in 1 L of 0.9% saline was continuously
circulated through the bundles using a peristaltic flow pump, and flow
rates were varied from 10 to 50 mL ·
min-1. The PI was varied from 200 to 3000 ms. In
one experiment, the concentration of microbubbles was varied while the
flow was held constant at 30 mL · min-1.
The concentrations of microbubbles in all these experiments did not
result in system saturation or attenuation at any PI.
In Vivo Experiments
In group 1 dogs (n=7), the purpose was to define the relation between
coronary flow and mean microbubble velocity in a setting in
which CBV remains relatively constant. A model with an incised
coronary artery (Fig 3B
In group 2 dogs (n=5), the purpose was to define the relation between
MCE and radiolabeled microsphere–derived MBF in which MBF is
altered solely through changes induced in CBV. Accordingly, proximal
segments of both the LAD and LCx were dissected free from surrounding
tissue. Time-of-flight flow probes (series SB; Transonics) were placed
around both vessels, and a 20-gauge catheter (Critikon) was introduced
into the LAD via a side branch (Fig 4A
In group 3 dogs (n=9), the purpose was to determine whether MCE-derived
MBF can be used to quantify coronary stenosis severity
both at rest and in the presence of coronary hyperemia.
Accordingly, these dogs underwent coronary artery dissection
similar to that in the group 2 dogs, except that a branch of either the
LAD or LCx was cannulated for measurement of distal coronary
pressure (Fig 4B
For MCE, the infusate consisted of 2 mL of MRX-115 in 25 mL of 0.9%
saline administered via the femoral vein. This infusion rate resulted
in excellent myocardial opacification without saturation or attenuation
in any dogs. As soon as a steady state from the infusion of
microbubbles was achieved, the imaging protocol, which consists of a
sequence of different PI, was initiated. The "imaging" trigger was
set to the T wave of the ECG signal (end systole
representing the smallest cavity size in the cardiac
cycle), whereas the "bubble destruction" trigger was set to
different intervals before the imaging trigger. Although both triggers
resulted in the production of images that potentially could
show myocardial opacification, VI measurements were made only from
images captured in end systole.15 In three dogs, data were
also collected with the imaging trigger set to end diastole
(peak of the R wave). Regions of interest for the LAD and LCx beds were
placed at the same image depth (
To confirm that the infusions were indeed constant,
background-subtracted LV and myocardial VI measurements were performed
in three group 1 dogs over 5 minutes and in one group 2 dog over 12
minutes using a PI that has been shown to cause negligible bubble
destruction (>1000 ms).9 The concentration of
microbubbles used for the LV VI determinations were lower than that
used for the myocardium to ensure that the microbubble
concentration versus VI relation was in the linear range.
The relation between VI and microbubble concentration in both the LV
cavity and myocardium was evaluated in one dog. The
microbubble concentration was slowly increased by changing the infusion
rate of a dilute solution of MRX-115 (4 mL in 96 mL of 0.9% saline)
from 0.08 to 6.7 mL · min-1 in small
increments. Imaging was performed with gating to every eighth cardiac
cycle (PI of 4.2±0.3 seconds).
Statistical Methods
Fig 5
In Vitro Experiments
Fig 7
In Vivo Experiments
Fig 9
Fig 10A
These results pertain to imaging in end systole only. In the three dogs
in which imaging was also performed in end diastole, no
differences were found between the value of ß derived at end systole
or end diastole. Because the interval between the "bubble
destruction" and "imaging" pulses can span several cardiac
cycles, the rate of replenishment of the ultrasound beam elevation by
microbubbles reflects an average of that from different phases of the
cardiac cycle, which can explain these findings.
MBF was increased in group 2 dogs solely by increasing CBV via
intracoronary infusion of vasodilators (adenosine and
acetylcholine). The doses of the drugs infused were sufficient to
increase LAD flow without any changes in LCx flow or mean
arterial pressure (Table 2
The protocol could not be completed in one group 3 dog due to
hemodynamic instability, and the distal
coronary catheter resulted in a myocardial infarction in
another dog, so the data from the remaining seven dogs are
presented in Table 3
In the presence of exogenously induced hyperemia with
WRC-0470, there were no significant changes in mean aortic pressure or
heart rate at any stage compared with the corresponding baseline stage.
As expected, the pressure gradient across the stenosis
increased significantly (P<.001) in the presence of
hyperemia compared with baseline, and this increase was higher
for more severe stenoses. MBF to the stenosed bed also
increased in all stages with hyperemia, but the maximal
hyperemic flow attained before placement of a stenosis
was significantly greater (P<.01) than that during either
stenosis stage. An excellent correlation was found between ß
and radiolabeled microsphere–derived MBF for all dogs (mean,
r=.93; range, .70 to .99). The value of A from
the stenosed bed was lower (P=.05) compared with the
control bed with increasing levels of stenosis. The correlation
between radiolabeled microsphere–derived MBF and MCE-derived
MBF (Aß) for all dogs was excellent (average,
r=.93; range, .71 to .99). As shown in Fig 12B
Ultrasound systems have a threshold below which microbubbles are not
detected.13 This threshold results from
suppression of electronic "noise," a narrow dynamic range, and
compression of the signal to display it on the video monitor. To be
detected in the myocardium, therefore, the concentration of
microbubbles in the LV cavity must be very high. Because the number of
microbubbles in the myocardium is much lower than that in
the LV cavity, the threshold effect makes the time-intensity curve from
the myocardium appear narrower than that from the LV
cavity.13 This phenomenon makes it impossible to
deconvolve the latter from the former, precluding the measurement of
the MBF/CBV relation during venous infusion of microbubbles.
Even if the threshold effect were not present, the transit rate of
intravenously administered microbubbles would not reflect
their dispersion through the myocardium. Microbubbles
injected into a peripheral vein first disperse through the
cardiac chambers and pulmonary vasculature before reaching the
coronary circulation. Compared with the central circulation,
further dispersion of the bubbles through the much smaller
coronary circulation is therefore insignificant. Consequently,
the resulting output function is not much different from the input
function,4 and this difference cannot be resolved
by ultrasound. Thus, the measured myocardial output function invariably
reflects the dispersion of bubbles in the large central circulation
(and hence provides a measure of cardiac
output16 ) rather than the mean myocardial transit
rate.4
Advantages of Our New Approach
The independent estimation of both microbubble velocity and
microvascular CSA afforded by our approach also has many advantages, as
demonstrated in our study. In situations in which MBF changes are not
associated with alterations in CBV, such as in the group 1 dogs, the
plateau VI did not change and alterations in MBF were reflected only by
changes in microbubble velocity. Similarly, in situations in which MBF
changes are associated with changes in CBV but not MBV, the plateau VI
should not change. The two examples of this phenomenon in our study
occurred during direct coronary infusion of vasodilators in the
group 2 dogs and in the presence of non–flow-limiting stenosis
at rest in the group 3 dogs. In both instances, reliance on changes in
VI alone would have led to errors in the estimation of MBF.
An interesting observation from this study is that when vasodilators
were infused directly into a coronary artery, increases in MBF
and microbubble velocity were not associated with changes in myocardial
microvascular CSA. These real-time in vivo results are identical to
those of Crystal et al18 and Eliasen and
Amtorp.19 In their experiments, the mean
myocardial transit rate of red blood cells increased during
adenosine infusion, implying that the increase in MBF occurred
via increase in CBV, but no changes in MBV were found. The microvessels
that are imaged within the myocardium and that constitute
MBV are predominantly capillaries,17 with
dimensions or numbers that are not altered by direct coronary
infusion of adenosine. Taken together, the results of these
studies indicate that direct coronary injection of
adenosine increases MBF by dilating microvessels which form a
small portion of the MBV or are not present within the myocardia. Thus,
by determining both CBV (measurement of the mean transit rate of
microbubbles after an intracoronary bolus
injection1 2 ) and MBV (measurement of
microvascular CSA during an intravenous infusion of
microbubbles), MCE could be used to separate changes in capillary
dimension or density from those of larger microvessels.
In the presence of coronary stenoses, both
microvascular CSA and microbubble velocity were found to be less in the
stenosed versus the normal bed during hyperemia. These findings
supports those of Canty et al,20 who measured
changes in MBV with the use of computed tomography. In the presence of
coronary hyperemia, arteriolar dimensions increase with
a consequent increase in MBF. In the stenotic bed, however,
hyperemia is associated with an increase in the resistance
across the bed compared with when no stenosis is present.
Thus, a partial collapse of microvessels is likely to occur distal to
the arterioles.6 Our results indicate that one
potential site of this phenomenon is the capillary bed.
From the ex vivo experiments, we showed that differences in flow
velocity can be detected using a single PI. This approach, however, has
two limitations. First, because the magnitude of MBF and the degree of
MBF mismatch between beds are not known a priori, the PI used may
not be optimal to display the maximal disparity in MBF between the
beds. As shown in the ex vivo experiment (Fig 5
Critique of Our Method
An alternative method for deriving MBV or microvascular CSA is depicted
in Fig 8
Because the ultrasound beam profile is not homogeneous
along its entire length, it is essential to have the exact value of the
beam elevation at all image depths in order to quantify microbubble
velocity. This value can be calibrated at different depths using an in
vitro system in which both the flow and CSA are known. It may also be
possible to "defocus" the beam or alter its profile so the beam
thickness becomes more uniform at all depths. In this manner, MBF can
be compared from different myocardial beds. We attempted to standardize
our comparisons by choosing regions of interest at similar imaging
depths.
Cardiac translation, caused by base-to-apex systolic
shortening, results in different short-axis planes of the heart being
imaged at different times in the cardiac cycle. If imaging is performed
using apical views, there also is counterclockwise rotation of the
heart during systole. Thus, in either view, the plane in which
microbubble destruction occurs may not be precisely the same in which
imaging subsequently occurs. This problem can be avoided if both
microbubble destruction and imaging are performed at the same point in
the cardiac cycle. The entire PI versus VI curve can potentially be
constructed using PIs that are multiples of one cardiac cycle.
Microbubble destruction and imaging will then occur in the same phase
of the cardiac cycle (either end diastole or end systole).
Quiet respiration can be used to minimize cardiac motion caused by
respiration, and images from the same part of the respiratory cycle can
be selected for analysis.
Several PIs are required to derive values for A and ß,
necessitating several minutes of image acquisition, which makes it
essential for systemic hemodynamics and MBF to be
stable for a long period. Thus, to produce steady state
hyperemia, we selected an intravenous infusion of
an adenosine agonist rather than a single venous injection of
dipyridamole, because peak hyperemia may not be
sustained by the letter. Such an approach may be indicated in the
clinical setting as well.
The VI versus PI relations in this study are based on a steady state of
microbubble concentration. Unlike a bolus administration of a large
dose of microbubbles, in which recirculation of microbubbles is
seen,4 5 6 prolonged infusions at low
concentrations do not change either LV cavity or myocardial VI. It is
possible that at these concentrations, the
reticuloendothelial system is able to clear the
microbubbles from the circulation at a rate that is similar to their
intravascular replenishment. Even if a small number of microbubbles
escape entrapment, they may not be sufficient to cause an appreciable
change in myocardial VI.
Given the <1-mm axial resolution of
echocardiography, it may be possible to measure the
transmural distribution of MBF. Such an analysis will need the
incorporation of both A and ß because VI measurements
alone were shown not to represent transmural distribution of
MBF.22 The exception to this finding is the
situation on which there is damage of the microvessels, so changes in
MBF are simply due to changes in microvascular
density.23 Similarly, phasic changes in MBF could
also be estimated using this technique if short PI or narrow-beam
elevations are used. Abnormalities in phasic changes in MBF may make it
possible to detect coronary stenosis at rest without
recourse to provocative
testing.24
Conclusions
Received July 7, 1997;
revision received September 30, 1997;
accepted September 30, 1997.
2.
Lindner JR, Skyba DS, Goodman NC, Jayaweera AR, Kaul
S. Changes in myocardial blood volume with graded coronary
stenosis. Am J Physiol. 1997;272:H567–H57.
3.
Albers VM. Underwater Acoustic Handbook.
State College, Pa: The Pennsylvania State University Press; 1960.
4.
Firschke C, Lindner JR, Wei K, Goodman NC, Skyba DM,
Kaul S. Myocardial perfusion imaging in the setting of coronary
artery stenosis and acute myocardial infarction using venous
injection of a second-generation echocardiographic
contrast agent. Circulation. 1997;96:959–967.
5.
Lindner JR, Firschke C, Wei K, Goodman NC, Skyba DM,
Kaul S. Myocardial perfusion characteristics and
hemodynamic profile of MRX-115, a venous
echocardiographic contrast agent, during acute
myocardial infarction. J Am Soc Echocardiogr. In press.
6.
Wei K, Firoozan S, Jayaweera AR, Linka A, Kaul S.
Detection of coronary stenosis from venous administration of
microbubbles: Bolus injection or continuous infusion?
Circulation. 1997;96(suppl I)I-213. Abstract.
7.
Kaul S, Senior R, Dittrich H, Raval U, Khattar R,
Lahiri A. Detection of coronary artery disease using myocardial
contrast echocardiography: comparison with
99mTc-Sestamibi single-photon emission computed
tomography. Circulation. 1997;96:785–792.
8.
Porter TR, Xie F, Kricsfeld D, Armbruster RW. Improved
myocardial contrast with second harmonic transient response imaging in
humans using intravenous perfluorocarbon-exposed sonicated
dextrose albumin. J Am Coll Cardiol. 1996;27:1497–1501.[Abstract]
9.
Wei K, Skyba DM, Firschke C, Lindner JR, Jayaweera AR,
Kaul S. Interaction between microbubbles and ultrasound: in vitro and
in vivo observations. J Am Coll Cardiol. 1997;29:1081–1088.[Abstract]
10.
Schrope B, Newhouse VL, Uhlendorf V. Simulated
capillary blood flow measurement using a non-linear ultrasonic contrast
agent. Ultrason Imaging. 1992;14:134–158.[Medline]
[Order article via Infotrieve]
11.
de Jong N. Higher harmonics of vibrating gas-filled
microspheres. In: de Jong N, ed. Acoustic Properties of
Ultrasound Contrast Agents. The Netherlands: Woerden, Zuidam and
Zonen bv; 1993:61–78.
12.
Burns PN, Powers JE, Simpson DH, Uhlendorf V,
Fritzsche T. Harmonic imaging with ultrasound contrast agents.
Clin Radiol. 1996;51(suppl):50–55.
13.
Skyba DM, Jayaweera AR, Goodman NC, Ismail S, Camarano
GP, Kaul S. Quantification of myocardial perfusion with myocardial
contrast echocardiography from left atrial
injection of contrast: implications for venous injection.
Circulation. 1994;90:1513–1521.
14.
Glover DK, Ruiz M, Yang JY, Koplan BA, Allen TR, Smith
WH, Watson DD, Barrett RJ, Beller GA. Pharmacological stress thallium
scintigraphy with
2-cyclohexylmethylidene-hydrazinoadenosine (WRC-0470): a novel,
short-acting adenosine A2A receptor
agonist. Circulation. 1996;94:1726–1732.
15.
Jayaweera AR, Sklenar J, Kaul S. Quantification of
images obtained during myocardial contrast
echocardiography.
Echocardiography. 1994;11:385–396.[Medline]
[Order article via Infotrieve]
16.
Galanti G, Jayaweera AR, Villanueva FS, Glasheen WP,
Ismail S, Kaul S. Transpulmonary transit of microbubbles during
contrast echocardiography: implications for
estimating cardiac output and pulmonary blood volume.
J Am Soc Echocardiogr. 1993;6:272–278.[Medline]
[Order article via Infotrieve]
17.
Kassab GS, Lin DH, Fung Y-CB. Morphometry of pig
coronary venous system. Am J Physiol. 1994;267:H2100–H2113.
18.
Crystal GJ, Downey HF, Bashour F. Small vessel and
total coronary blood volume during intracoronary
adenosine. Am J Physiol. 1981;241:H194–H201.
19.
Eliasen P, Amtorp O. Effect of intracoronary
adenosine upon regional blood flow, microvascular blood volume
and hematocrit in canine myocardium. Int J
Microcirc. 1984;3:3–12.[Medline]
[Order article via Infotrieve]
20.
Canty JM, Judd RM, Brody AS, Klocke FJ. First-pass
entry of nonionic contrast agent into the myocardial extravascular
space: effects on radiographic estimates of transit time
and blood volume. Circulation. 1991;84:2071–81.
21.
Wang T, Wu X, Chung N, Ritman EL. Myocardial blood flow
estimated by synchronous, multislice, high-speed computed tomography.
IEEE Trans Med Imag. 1989;8:70–77.[Medline]
[Order article via Infotrieve]
22.
Kaul S, Jayaweera AR, Glasheen WP, Villanueva FS,
Gutgessel HP, Spotnitz WD. Myocardial contrast
echocardiography and the transmural distribution of
flow: a critical appraisal during myocardial ischemia not
associated with infarction. J Am Coll Cardiol. 1992;20:1005–1016.[Abstract]
23.
Villanueva FS, Glasheen WP, Sklenar J, Kaul S.
Assessment of risk area during coronary occlusion and infarct
size after reperfusion with myocardial contrast
echocardiography using left and right atrial
injections of contrast. Circulation. 1993;88:596–604.
24.
Kern MJ, Aguirra F, Bach RG, Donohue TJ, Caraccilo E.
Restoration of normal phasic flow velocity after multiple
coronary artery stent placement. Am Heart J. 1994;127:204–207.[Medline]
[Order article via Infotrieve]
© 1998 American Heart Association, Inc.
Basic Science Reports
Quantification of Myocardial Blood Flow With Ultrasound-Induced Destruction of Microbubbles Administered as a Constant Venous Infusion
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
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.
Key Words: echocardiography • contrast media • blood flow • microcirculation
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
We have previously
shown that the relation between MBF and total CBV can be quantified
with MCE.1 2 CBV includes the blood volume from
epicardial conduit arteries, arterioles, capillaries, venules, and
veins. When sonicated albumin microbubbles were injected
directly into a coronary artery,1 2
changes in the mean myocardial transit rates were found to reflect
changes in the MBF/CBV relation, which is consistent with
classic indicator dilution principles. This approach is limited,
however, because alterations in the mean microbubble transit rate
reflect relative rather than absolute changes in MBF or CBV. It is not
possible to quantify one without knowing the other. The need to use
intracoronary injections also limits the clinical applications
of this technique.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Model Development
Assume, first, that microbubbles are administered
intravenously as a continuous infusion at a constant rate
and concentration. After steady state is achieved, assume that all
microbubbles within an ultrasound field are destroyed by a single
ultrasound pulse (Fig 1
) and that the
elevation (thickness) of the ultrasound beam E is uniform.
If new microbubbles enter this field with a flat profile at a velocity
v, then the distance (d) they will travel within
the beam elevation (Fig 1B through 1E) will be given by the following
equation:
where t is the PI of ultrasound.
(1)
View larger version (18K):
[in a new window]
Figure 1. The elevation (thickness) of the ultrasound beam
is represented as E (A). If all the microbubbles in the
elevation are destroyed by a single pulse of ultrasound at
t0, then replenishment of the beam elevation
(d1 through d4, B through E), will depend on
the velocity of microbubbles and the ultrasound PI t. See text for
details. 
, VI is
proportional to vt/E. At a constant v, VI
increases with t until a specific PI, T, is
reached (Fig 2A), at which the
microbubbles have just sufficient time to fill the entire beam
thickness (Fig 1E). Then,
As shown in Fig 2A
(2) , when the PI exceeds T, VI will
remain constant. This plateau phase will reflect the effective
microbubble concentration within the myocardial microcirculation. At
any given concentration of intravenously infused
microbubbles, the VI at the plateau phase will be proportional to the
sum of CSA of microvessels (a) within the beam
thickness.
View larger version (13K):
[in a new window]
Figure 2. The PI (x axis) versus VI
(y axis) relation as (A) predicted by the model and (B)
observed experimentally. The function is used to derive
parameters A and ß. See text for details. ). In reality, however, neither the
beam elevation nor the degree of microbubble destruction are expected
to be entirely uniform. The profile of the microbubbles also is not
expected to be entirely flat. The actual relation between VI and PI is
therefore more likely to be curvilinear as shown in Fig 2B and can be
described by the following exponential function:
where y is VI at a PI t, A is
the plateau VI, and ß is the rate constant that determines the rate
of rise of VI.
(3) , this slope is also equal to A/T.
Therefore,
Eliminating T between equations 2
(4) , and 4 results
in:
Thus, for a given beam elevation (thickness at a given
distance from the transducer), the mean velocity of microbubbles is
proportional to ß. If flow, f, occurs through an area,
a, then:
(5)
If E is constant, then a will be
proportional to A. Therefore, with rearrangement of equation 6
(6) and substituting for v from equation 5, we get:
When E is constant,
(7)
From equation 5
(8) it is obvious that if E is known,
then v can be expressed in cm ·
s-1. Similarly, if the microvascular CSA is
known, then A can be expressed in cm2.
The product of A and v will then
represent f in mL ·
s-1.
Ex vivo experiments with explanted veins were initially
performed to determine the efficacy of microbubble destruction in a
flowing system and to evaluate the optimal PI required to detect flow
differences from VI measurements. Because of the large CSA and low
resistance of the ex vivo veins, the flow rates used were much higher
than those in the microcirculation. To evaluate flow rates seen within
the myocardium, in vitro experiments were performed with
hollow-fiber bundles that had CSA more akin to that of microvessels.
This system was also used to derive the PI versus VI relation at
multiple flow rates. To test the model in vivo, we first used an
experimental setup in which MBF could be altered without changing CBV.
Subsequently, a preparation was used in which changes in MBF were
caused solely by changes in CBV. Finally, a coronary
stenosis model that more closely resembles the clinical
situation was used.
Image Acquisition
A prototype Sonos 2500 system (Hewlett Packard) was used for
these experiments. All imaging was performed in harmonic mode, in which
ultrasound was transmitted at 2 MHz and received at 4 MHz. Ultrasound
pulses were gated to an internal timer for the ex vivo and in vitro
experiments or to the ECG signal for in vivo experiments. Dual
triggering, which allows ultrasound to be transmitted twice within an
RR interval, also was used for in vivo experiments to generate short
PI. The rationale was to destroy bubbles during the first ultrasound
pulse and to image their reappearance within the myocardium
with the second pulse. During an imaging sequence, the interval between
these pulses was progressively prolonged to allow more bubble
replenishment of the ultrasound beam elevation.
A second-generation microbubble solution (MRX-115; ImaRx
Pharmaceutical) was used in this study and was administered as a
continuous infusion in all experiments. The microbubbles have a mean
size of 2.5 µm and a concentration of
1.2x109 · mL-1.
They have an 8-nm bilayer phospholipid shell and are filled with a
mixture of air and perfluoropropane. These microbubbles have been shown
to have no effect on systemic hemodynamics or
pulmonary gas exchange.5
All catheters were connected to fluid-filled pressure
transducers, which, like the flowmeter, were connected to a
multichannel recorder (model ES2000; Gould Electronics). Epicardial
coronary artery flows and all pressure signals were acquired
digitally at 200 Hz into an 80386-based personal computer via an
eight-channel analog-to-digital convertor (Metrabyte). The signals were
displayed on-line using Labtech Notebook (Laboratory
Technologies).2
Conduit Flow
Flows in the tubing for the ex vivo and in vitro experiments, as
well as to the LAD in the group 1 dogs, were controlled with
peristaltic pumps (model 2501–001; Harvard Apparatus,
and/or model S10K 2, Sarns Inc). They were measured using
time-of-flight ultrasonic flow probes placed directly on the tubing
(Series SC, Transonics) or the LAD (Series SB, Transonics).
In group 2 and 3 dogs, the radiolabeled microsphere
technique was used as the gold standard for measuring MBF. It was
determined by left atrial injection of 
2x106
11-µm radiolabeled microspheres (Dupont Medical Products)
suspended in a solution of 4 mL of 0.9% saline and 0.01%
Tween-80.1 2 Duplicate reference samples were
withdrawn from the femoral arteries over 130 seconds with a
constant-rate withdrawal pump (model 944; Harvard
Apparatus).
Ex Vivo Experiments
The aims of these experiments were to demonstrate (1) the
efficacy of microbubble destruction by ultrasound in a flow system and
(2) the influence of the PI on the detection of flow differences from
VI measurements. Fig 3A illustrates our
experimental setup. Two segments of external jugular vein (0.8 cm in
diameter) obtained from dogs were attached to two separate pieces of
100-cm-long tubing and immersed side-by-side within a water bath. The
distance between the veins and transducer was held constant throughout
the experiment. The same solution of MRX-115 was circulated
continuously through both veins using separate pumps.
View larger version (20K):
[in a new window]
Figure 3. A, Ex vivo experimental setup. B, Animal
preparation used for the group 1 dogs.
The purpose of these experiments was to determine (1) the
VI-versus-PI relation for different flow rates and (2) the effect of
different microbubble concentrations on the determination of
A and ß at the same flow rate. The experiments were
performed using hollow hemodialysis fiber bundles (Spectra/Por;
Spectrum Microgon). A single bundle consists of 352 fibers, each
200 µm in diameter, which is similar to the diameter of the
larger myocardial microvessels. Four bundles were attached to tubing
and immersed in parallel in a 0.9% saline bath at a fixed distance
from the ultrasound transducer.
The study protocols were approved by the Animal Research
Committee at the University of Virginia and conformed to the American
Heart Association Guidelines for Use of Animals in Research. A total of
21 dogs were used for the experiments. They were anesthetized
with 30 mg · kg-1 sodium pentobarbital
(Abbott Laboratories), intubated, and ventilated with a respirator pump
(model 607; Harvard Apparatus). Fluid was administered via
7F catheters placed in the femoral veins. A left lateral thoracotomy
was performed, and the heart was suspended in a pericardial cradle. ) was therefore chosen because
autoregulation is virtually abolished in this
model.1 Accordingly, the proximal LAD was
dissected free from the surrounding tissues. A cannula was inserted
into the left carotid artery and connected to tubing that was attached
to another cannula. After ligation of the LAD, this cannula was
inserted into it and secured in place. Flow through the tubing was
controlled using a peristaltic flow pump (model 2501–001; Harvard
Apparatus) and measured using an extracorporeal
time-of-flight ultrasonic flow probe (series SC; Transonics) connected
to a digital flowmeter (model T206; Transonics). The LAD flow was
adjusted to four to five levels in a random order. ).
To change MBF, vasodilators were administered directly into the LAD
through this catheter using a constant-rate infusion pump (model 944;
Harvard Apparatus). Adenosine (Sigma Chemical) was
infused at rates of 2.5 µg · kg-1
· min-1 (low dose) and 5.0 µg ·
kg-1 · min-1 (high
dose), and acetylcholine (Sigma Chemical Co.) was infused at a rate of
0.3 µg · kg-1 ·
min-1. During the administration of each drug,
MCE was initiated only after the LAD flow had stabilized. It was
allowed to return to baseline for 
5 minutes before the next dose/drug
was administered. Arterial pressure was monitored via a
catheter in the femoral artery.
View larger version (23K):
[in a new window]
Figure 4. Animal preparations used for the (A) group 2 dogs
and (B) group 3 dogs. ). A screw occluder was placed around the vessel to
create coronary stenoses of various
severities.2 The severity of a stenosis
was judged by the gradient between the central aortic and distal
coronary pressure. Three stages were used: baseline and two
different degrees of stenoses, which were not flow limiting at
rest. At each stage, MCE was performed both before and during an
intravenous infusion of WRC-0470, a novel adenosine
A2a receptor agonist that causes coronary
hyperemia without significant systemic
hemodynamic effects.14 9 to 11 o'clock position for the
LAD and 1 to 3 o'clock position for the LCx).
Comparisons between more than two stages were performed with
repeated measures ANOVA, whereas those between two stages were made
with Student's t test. All correlations were performed
using least-squares linear regression analysis. Differences
were considered significant at P<.05.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Ex Vivo Experiments
Table 1 depicts the efficacy of
ultrasound in destroying microbubbles in a flowing system. The number
of microbubbles from just proximal and distal to the transducer
location were similar when no ultrasound was transmitted. At PI of 33
and 200 ms, virtually no bubbles were seen distal to the transducer.
When the PI was increased to 1000 ms, bubble destruction was less.
View this table:
[in a new window]
Table 1. Number of Microbubbles Proximal and Distal to
Transducer in Ex Vivo Experiments illustrates the importance of using
the correct PI for the detection of flow differences based on VI
measurements. Although the concentration of microbubbles in both veins
was identical, there was a fourfold difference in the flow between the
two veins. Fig 5A and 5B depict images acquired at PI of 33 and 200 ms,
respectively. At the short PI, more bubbles have replenished the
ultrasound beam elevation in the vein with higher compared with lower
flow (Fig 5A), allowing for flow differences in the two veins to be
noted. In comparison, when the PI was prolonged, the bubbles completely
replenished the ultrasound beam elevation in both veins, and flow
differences in the two veins were no longer seen (Fig 5B). Obviously,
the optimal PI for distinguishing different flows depends on the flow
rates themselves.
View larger version (23K):
[in a new window]
Figure 5. Effect of PI on measured VI in the ex vivo
experiment. The vein on the left has one fourth of the flow compared
with the vein on the right. The concentration of microbubbles is the
same for both veins. More replenishment of microbubbles into the vein
with higher flow is seen using a short PI (A), resulting in greater VI
disparity between the two veins. When sufficient time is allowed for
microbubbles to replenish the beam elevation even in the vein with low
flow (B), the VI disparity between the veins is no longer seen. See
text for details.
Fig 6 illustrates the PI versus VI
relations at different flow rates in the hollow fiber bundles. It is
obvious that for any flow, several PIs were required to derive the
values of ß and A. VI increased more rapidly and reached a
plateau at a shorter PI when flows were higher (Fig 6A). An excellent
linear relation was noted between the value ß from the fitted
functions and flow measured in the tubing (Fig 6B).
View larger version (19K):
[in a new window]
Figure 6. A, PI (x axis) versus VI
(y axis) relation at four different flow rates in the in
vitro experiments. B, Relation between absolute flow (x
axis) and the rate constant ß from each of the fitted functions in A
(y axis). See text for details. depicts VI data using solutions
with three different microbubble concentrations at a constant flow rate
of 30 mL · min-1. Two important points
are evident from these data. First, as long as the relation between
microbubble concentration and VI remains within the linear
range,13 ß reflects velocity and is not
affected by the concentration of microbubbles infused
intravenously. Second, because changing microbubble
concentration within the fibers is equivalent to changing the number of
fibers containing the same concentration of microbubbles, these results
indicate that the measurement of A actually reflects fiber
CSA.
View larger version (15K):
[in a new window]
Figure 7. Effect of microbubble concentration on the rate
constant ß and the plateau VI at a constant flow rate of 30 mL
· min-1. The plateau VI increases with the increasing
concentration of microbubbles, but the rate constant ß does
not.
Using a PI >1000 ms, both myocardial and LV video intensities
remained unchanged during constant infusions of microbubbles over 5 to
12 minutes. The relations between VI and infusion rate (which denotes
microbubble concentration) for both the LV cavity and
myocardium are shown in Fig 8. There was an initial rapid rise of VI
in the LV cavity as microbubble concentration increased. As the
concentration continued to increase, however, the LV VI reached a
plateau. Appreciable myocardial opacification was noted only during
this plateau phase when microbubble concentration in the LV cavity was
high. When the linear portion of the relation between microbubble
concentration and VI from the LV cavity was extrapolated to the level
at which myocardial VI was similar to that noted in this study, the
myocardial/LV cavity VI ratio was 8%. Because the LV cavity contains
only blood, these data indicate that the estimated MBV is 8%. Thus,
despite the nonlinear relation between microbubble concentration and
VI, myocardial VI can be calibrated as a percentage of the VI in the LV
cavity.
View larger version (21K):
[in a new window]
Figure 8. Microbubble concentration (x axis)
versus VI (y axis) relation for both the LV cavity ( 
)
and myocardium (
). Extrapolation of the initial linear
portion of the LV cavity relation (dashed line) allows the "expected
LV cavity VI" at any microbubble concentration to be estimated. The
MBV fraction may be calculated as the ratio between the myocardial VI
and the extrapolated LV cavity VI (dotted line). See text for
details. depicts images obtained at a
constant LAD flow of 65 mL · min-1 at
four incremental PIs in one group 1 dog. The color-coding algorithm
used to illustrate the data has been described
previously.15 Shades of red, progressing to hues
of orange, yellow, and then white, represent incremental
myocardial contrast opacification. At the shortest PI, no contrast was
seen in either the LAD or LCx beds, indicating that the PI was too
short to allow replenishment of detectable amounts of microbubbles in
either bed. At a higher PI, the VI in the LAD bed increased
progressively and reached a plateau at longer PI. Initial opacification
of the LCx bed was seen at a higher PI than the LAD bed, and its rate
of rise is also slower, indicating a lower microbubble velocity in the
LCx bed.
View larger version (111K):
[in a new window]
Figure 9. End-systolic images at a constant LAD flow
of 65 mL · min-1 at four PIs (316, 536, 1608, and
5360 ms in A through D, respectively). At the shortest PI, no contrast
can be seen in either LAD or LCx beds, indicating that the PI was too
short to allow replenishment of measurable numbers of microbubbles into
either bed. VI in the LAD bed progressively increases with increasing
PI and plateaus at an interval of 5360 ms. To obtain these color-coded
images, three averaged precontrast frames were digitally subtracted
from three averaged postcontrast frames at each PI. The VI scale of the
resulting subtracted image was expanded to a dynamic range of 128 gray
levels, in which the pixel showing the greatest contrast change was
assigned a value of 128, and all others were assigned proportionally
lower values. All pixels with a gray scale value of >10 were assigned
a color based on the degree of contrast enhancement. Shades of red to
yellow to orange to white denote greater video intensities. See text
for details. illustrates the VI versus PI
plots from the LAD bed at five different flows in one dog. As the LAD
flow was increased, the value of ß also increased. Fig 10B shows the
excellent relation between ß and LAD flow in the same dog. Similar
results were found in all other dogs (Fig 11) with an average correlation between
ß and mean coronary flow in all seven dogs of
r=.91 (range, .77 to .97).
View larger version (19K):
[in a new window]
Figure 10. A, Relation between PI (x
axis) and VI (y axis) at five different flow rates from
a group 1 dog. B, Relation between the epicardial flow
(x axis) and the rate constant ß derived from the
fitted functions (y axis) in A for the same dog. See
text for details.
View larger version (24K):
[in a new window]
Figure 11. Relation between absolute epicardial flow
(x axis) and ß for the other six group 1 dogs. The
average correlation for all seven group 1 dogs was
r=.91. See text for details. ).
During peak hyperemia, both LAD flow and radiolabeled
microsphere-derived MBF in the LAD bed increased approximately
threefold compared with baseline. An excellent correlation was found in
all dogs between the value of ß and LAD flow as well as radiolabeled
microsphere-derived MBF in the LAD bed (r=.88,
P<.001). Despite large increases in MBF caused by the
vasodilators, no significant change in A was found,
indicating that microvascular CSA within the myocardium did
not change appreciably (Table 2). As shown in Fig 12A, the relation between radiolabeled
microsphere–derived MBF and MCE derived MBF (Aß)
was excellent.
View this table:
[in a new window]
Table 2. Hemodynamic, MBF, and MCE Data in
Group 2 Dogs
View larger version (17K):
[in a new window]
Figure 12. A, Relation between radiolabeled
microsphere–derived myocardial blood flow
(x axis) and A · ß derived on MCE
(y axis) in the group 2 dogs. B, Relation between the
ratio of radiolabeled microsphere–derived myocardial blood
flow from the stenosed and nonstenosed beds (x axis) and
the A · ß ratio derived on MCE from the two beds
(y axis) in the group 3 dogs. See text for
details. . There were
three stages for each dog: baseline and two separate stenosis
stages. Before hyperemia, the pressure gradient across the
stenosis increased with increasing stenosis severity,
but MBF and all other hemodynamic data remained
unchanged. Likewise, the mean values of A, ß, and
Aß also did not change at any stage compared with the
nonstenosed bed. Thus, like MBF, microbubble velocity and myocardial
microvascular CSA remain constant at rest in the presence of
non–flow-limiting coronary stenosis.
View this table:
[in a new window]
Table 3. Hemodynamic, MBF, and MCE Data in
Group 3 Dogs Before and During Induction of Coronary
Hyperemia , an excellent
correlation was also found between the Aß ratio from the
stenosed versus normal bed and the radiolabeled
microsphere–derived MBF ratio from the two beds. All the
points lie practically on the line of identity except for two outliers
(
). In these two dogs, the value of A in the control bed
was artificially reduced as a result of lateral wall attenuation,
resulting in an apparent "increase" in the Aß ratio
compared with the stenosed bed.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Limitations in Using Tracer Kinetics to Measure Myocardial
Perfusion With MCE After Venous Administration of Microbubbles
When microbubbles are injected as a discrete bolus directly into a
coronary artery, their mean transit rate reflects the MBF/CBV
relation.1 2 When they are administered
intravenously, the input function of the
myocardium is the time-intensity curve from the LV cavity.
As a result of dispersion of the microbubbles through the myocardial
microvasculature, the myocardial output function should be wider than
the input function. A number of factors, however, make the myocardial
output function appear paradoxically narrower than the input
function.
The novelty of our approach is that it does not rely on tracer
kinetic principles to quantify myocardial perfusion. Destruction of
microbubbles and measurement of their reappearance rate within the
myocardium during a continuous infusion provide an
estimation of mean myocardial microbubble velocity. Similarly, the
plateau VI at long PI reflects microvascular CSA. The product of
the two provides an estimation of MBF. ), use of a PI that is
too short or too long may obscure VI disparities. Second, even if
optimally timed, a single PI can provide only an assessment of the
relative degree of flow mismatch. Multiple PIs are required to quantify
myocardial microbubble velocity.
We have shown that the myocardial microbubble velocity can be
derived from the PI versus VI relation during a continuous venous
infusion. Derivation of the absolute value of MBV or microvascular CSA,
however, is more involved. First, the VI within the
myocardium depends on the concentration of microbubbles
infused in the vein. Second, as shown in Fig 8, at concentrations
required to produce myocardial opacification, the relation between
microbubble concentration and VI within the LV cavity is no longer in
the linear range. Thus, unlike other
techniques,21 expression of myocardial VI as a
percentage of that obtained from the LV cavity does not provide an
accurate estimation of MBV with MCE. and is in the range reported with the use of other
methods.2 21 If the sizes of the regions of
interest and the ultrasound beam elevation are known, MBF can be
calculated in absolute terms. Let us assume that a
1-cm2 rectangular region of interest is placed
over the myocardium and that the ultrasound beam elevation
is 0.5 cm; therefore, the volume of tissue being examined is 0.5
cm3. Using the volume fraction of blood estimated
above, MBV will be 0.04 mL. The average myocardial microbubble velocity
at rest in our dogs was 0.6 cm · s-1.
Tissue flow as derived in equation 7 will therefore be 0.012 mL
· s-1, or 0.72 mL ·
min-1, which is consistent with values
derived using radiolabeled microspheres in these dogs.
We have defined a novel method for measuring microbubble velocity
and microvascular CSA that is based on bubble destruction by
ultrasound. Measurement of these variables provides a quantitative
assessment of MBF using a venous infusion of microbubbles, a technique
that is likely to become clinically feasible in the near future.
Although these data were derived from the myocardium, this
method can be applied to any tissue accessible to ultrasound and
therefore has the potential for quantifying perfusion in many organ
systems.
Selected Abbreviations and Acronyms
CBV
=
coronary blood volume
CSA
=
cross-sectional area
MBF
=
myocardial blood flow
MBV
=
myocardial blood volume
MCE
=
myocardial contrast echocardiography
LAD
=
left anterior descending coronary artery
LCx
=
left circumflex coronary artery
LV
=
left ventricular, ventricle
PI
=
pulsing interval
VI
=
video intensity
Acknowledgments
This work was supported in part by a grant from the National
Institutes of Health (R01-HL-48890 and a Grant-in-Aid from the American
Heart Association, Virginia Affiliate. It was also supported by a grant
from ImaRx Pharmaceutical Corp (Tucson, Ariz) and an equipment grant
from Hewlett Packard Corp (Andover, Mass). The radiolabeled
microspheres were provided as a grant from Dupont-Merck (North
Billerica, Mass). Dr Wei was the recipient of a Junior Personnel
Research Fellowship from the Heart and Stroke Foundation of Canada
(Ottawa, Canada), and Dr Firoozan was the recipient of a Junior
Research Fellowship from the British Heart Foundation (London, UK). Dr
Skyba is supported by postdoctoral fellowship grant F32-HL-095410 from
the National Institutes of Health, and Dr Kaul was an Established
Investigator of the American Heart Association, National Center. The
authors thank Patrick Rafter, MS (Hewlett Packard Corp) for his
invaluable assistance and for providing us with the ability to change
ultrasound PIs.
Footnotes
Presented in part at the Young Investigator Award Competition at the 46th Annual Scientific Sessions of the American College of Cardiology, March 1997, Anaheim, Calif, and in part at the 70th Annual Scientific Sessions of the American Heart Association, November 1997, Orlando, Fla.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Jayaweera AR, Edwards N, Glasheen WP, Villanueva
FS, Abbott RD, Kaul S. 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.
This article has been cited by other articles:
 |
|
 |
|
  S S Abdelmoneim, A Dhoble, M Bernier, S Moir, M E Hagen, S A C Ness, S S Abdel-Kader, P A Pellikka, and S L Mulvagh Absolute myocardial blood flow determination using real-time myocardial contrast echocardiography during adenosine stress: comparison with single-photon emission computed tomography Heart, October 15, 2009; 95(20): 1662 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Abdelmoneim, A. Dhoble, M. Bernier, P. J. Erwin, G. Korosoglou, R. Senior, S. Moir, I. Kowatsch, S. Xian-Hong, T. Muro, et al. Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies Eur J Echocardiogr, October 1, 2009; 10(7): 813 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Lonnebakken, E. M. Staal, O. Bleie, E. Strand, O. K. Nygard, and E. Gerdts Quantitative contrast stress echocardiography in assessment of restenosis after percutaneous coronary intervention in stable coronary artery disease Eur J Echocardiogr, October 1, 2009; 10(7): 858 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kalantarinia, J. T. Belcik, J. T. Patrie, and K. Wei Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound Am J Physiol Renal Physiol, October 1, 2009; 297(4): F1129 - F1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Salerno and G. A. Beller Noninvasive Assessment of Myocardial Perfusion Circ Cardiovasc Imaging, September 1, 2009; 2(5): 412 - 424. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Liu, J. Liu, L. A. Jahn, D. E. Fowler, and E. J. Barrett Infusing Lipid Raises Plasma Free Fatty Acids and Induces Insulin Resistance in Muscle Microvasculature J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3543 - 3549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Keske, L. H. Clerk, W. J. Price, L. A. Jahn, and E. J. Barrett Obesity Blunts Microvascular Recruitment in Human Forearm Muscle After a Mixed Meal Diabetes Care, September 1, 2009; 32(9): 1672 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kuliszewski, H. Fujii, C. Liao, A. H. Smith, A. Xie, J. R. Lindner, and H. Leong-Poi Molecular imaging of endothelial progenitor cell engraftment using contrast-enhanced ultrasound and targeted microbubbles Cardiovasc Res, September 1, 2009; 83(4): 653 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Qayum, R. J. Muschel, J. H. Im, L. Balathasan, C. J. Koch, S. Patel, W. G. McKenna, and E. J. Bernhard Tumor Vascular Changes Mediated by Inhibition of Oncogenic Signaling Cancer Res., August 1, 2009; 69(15): 6347 - 6354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaul and K. Wei When you have eliminated the impossible, whatever remains, however improbable, must be the truth Eur J Echocardiogr, August 1, 2009; 10(6): 713 - 715. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fujii, Z. Sun, S.-H. Li, J. Wu, S. Fazel, R. D. Weisel, H. Rakowski, J. Lindner, and R.-K. Li Ultrasound-Targeted Gene Delivery Induces Angiogenesis After a Myocardial Infarction in Mice J. Am. Coll. Cardiol. Img., July 1, 2009; 2(7): 869 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Sullivan, B. Wang, E. I. Boesen, G. D'Angelo, J. S. Pollock, and D. M. Pollock Novel use of ultrasound to examine regional blood flow in the mouse kidney Am J Physiol Renal Physiol, July 1, 2009; 297(1): F228 - F235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Womack, D. Peters, E. J. Barrett, S. Kaul, W. Price, and J. R. Lindner Abnormal skeletal muscle capillary recruitment during exercise in patients with type 2 diabetes mellitus and microvascular complications. J. Am. Coll. Cardiol., June 9, 2009; 53(23): 2175 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Lee and N. P. Johnson Quantification of Absolute Myocardial Blood Flow by Magnetic Resonance Perfusion Imaging J. Am. Coll. Cardiol. Img., June 1, 2009; 2(6): 761 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Bierig, P. Mikolajczak, S. C. Herrmann, N. Elmore, M. Kern, and A. J. Labovitz Comparison of myocardial contrast echocardiography derived myocardial perfusion reserve with invasive determination of coronary flow reserve Eur J Echocardiogr, March 1, 2009; 10(2): 250 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Senior, H. Becher, M. Monaghan, L. Agati, J. Zamorano, J. L. Vanoverschelde, and P. Nihoyannopoulos Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography Eur J Echocardiogr, March 1, 2009; 10(2): 194 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Dolan, S. S. Gala, S. Dodla, S. S. Abdelmoneim, F. Xie, D. Cloutier, M. Bierig, S. L. Mulvagh, T. R. Porter, and A. J. Labovitz Safety and efficacy of commercially available ultrasound contrast agents for rest and stress echocardiography a multicenter experience. J. Am. Coll. Cardiol., January 6, 2009; 53(1): 32 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jarnert, L. Landstedt-Hallin, K. Malmberg, A. Melcher, J. Ohrvik, H. Persson, and L. Ryden A randomized trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve: a report from the DADD (Diabetes mellitus And Diastolic Dysfunction) study Eur J Heart Fail, January 1, 2009; 11(1): 39 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Muniyappa, G. Hall, T. L Kolodziej, R. J Karne, S. K Crandon, and M. J Quon Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1685 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Loveless, X. Li, J. Huamani, A. Lyshchik, B. Dawant, D. Hallahan, J. C. Gore, and T. E. Yankeelov A Method for Assessing the Microvasculature in a Murine Tumor Model Using Contrast-Enhanced Ultrasonography J. Ultrasound Med., December 1, 2008; 27(12): 1699 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Sinusas, F. Bengel, M. Nahrendorf, F. H. Epstein, J. C. Wu, F. S. Villanueva, Z. A. Fayad, and R. J. Gropler Multimodality Cardiovascular Molecular Imaging, Part I Circ Cardiovasc Imaging, November 1, 2008; 1(3): 244 - 256. [Full Text] [PDF]
|
|
|
|
|
|
L. Afonso, K. Bachour, K. Awad, and G. Sandidge Takotsubo cardiomyopathy: pathogenetic insights and myocardial perfusion kinetics using myocardial contrast echocardiography Eur J Echocardiogr, November 1, 2008; 9(6): 849 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kaul Myocardial Contrast Echocardiography: A 25-Year Retrospective Circulation, July 15, 2008; 118(3): 291 - 308. [Full Text] [PDF]
|
|
|
|
|
|
C. Z. Behm, B. A. Kaufmann, C. Carr, M. Lankford, J. M. Sanders, C. E. Rose, S. Kaul, and J. R. Lindner Molecular Imaging of Endothelial Vascular Cell Adhesion Molecule-1 Expression and Inflammatory Cell Recruitment During Vasculogenesis and Ischemia-Mediated Arteriogenesis Circulation, June 3, 2008; 117(22): 2902 - 2911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Lindner, L. Womack, E. J. Barrett, J. Weltman, W. Price, N. L. Harthun, S. Kaul, and J. T. Patrie Limb stress-rest perfusion imaging with contrast ultrasound for the assessment of peripheral arterial disease severity. J. Am. Coll. Cardiol. Img., May 1, 2008; 1(3): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.A. Hayat, G. Dwivedi, A. Jacobsen, T.K. Lim, C. Kinsey, and R. Senior Effects of Left Bundle-Branch Block on Cardiac Structure, Function, Perfusion, and Perfusion Reserve: Implications for Myocardial Contrast Echocardiography Versus Radionuclide Perfusion Imaging for the Detection of Coronary Artery Disease Circulation, April 8, 2008; 117(14): 1832 - 1841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Miller, M. A. Averkiou, A. A. Brayman, E. C. Everbach, C. K. Holland, J. H. Wible Jr, and J. Wu Bioeffects Considerations for Diagnostic Ultrasound Contrast Agents J. Ultrasound Med., April 1, 2008; 27(4): 611 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Kaufmann, A. M. Bernheim, S. Kiencke, M. Fischler, J. Sklenar, H. Mairbaurl, M. Maggiorini, and H. P. Brunner-La Rocca Evidence supportive of impaired myocardial blood flow reserve at high altitude in subjects developing high-altitude pulmonary edema Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1651 - H1657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Clark, S. Rattigan, E. J. Barrett, and M. A. Vincent Point:Counterpoint: There is/is not capillary recruitment in active skeletal muscle during exercise J Appl Physiol, March 1, 2008; 104(3): 889 - 891. [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Wilson, H.-J. Jang, T. K. Kim, H. Iijima, N. Kamiyama, and P. N. Burns Real-Time Temporal Maximum-Intensity-Projection Imaging of Hepatic Lesions with Contrast-Enhanced Sonography Am. J. Roentgenol., March 1, 2008; 190(3): 691 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Grayburn and J. W. Choi Advances in the assessment of no-reflow after successful primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: now that we can diagnose it, what do we do about it? J. Am. Coll. Cardiol., February 5, 2008; 51(5): 566 - 568. [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hayat and R. Senior Myocardial contrast echocardiography in ST elevation myocardial infarction: ready for prime time? Eur. Heart J., February 1, 2008; 29(3): 299 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Willmann, R. Paulmurugan, K. Chen, O. Gheysens, M. Rodriguez-Porcel, A. M. Lutz, I. Y. Chen, X. Chen, and S. S. Gambhir US Imaging of Tumor Angiogenesis with Microbubbles Targeted to Vascular Endothelial Growth Factor Receptor Type 2 in Mice Radiology, February 1, 2008; 246(2): 508 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Ross, G. D. Wadley, M. G. Clark, S. Rattigan, and G. K. McConell Local Nitric Oxide Synthase Inhibition Reduces Skeletal Muscle Glucose Uptake but Not Capillary Blood Flow During In Situ Muscle Contraction in Rats Diabetes, December 1, 2007; 56(12): 2885 - 2892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Shah, P. Balan, M. Weinberg, V. Reddy, R. Neems, M. Feinstein, J. Dainauskas, P. Meyer, M. Goldin, and S. B. Feinstein Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vascular Medicine, November 1, 2007; 12(4): 291 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 Z. Liu Insulin at physiological concentrations increases microvascular perfusion in human myocardium Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1250 - E1255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. I I Soliman, P. Knaapen, M. L Geleijnse, P. A Dijkmans, A. M Anwar, A. Nemes, M. Michels, W. B Vletter, A. A Lammertsma, and F. J ten Cate Assessment of intravascular and extravascular mechanisms of myocardial perfusion abnormalities in obstructive hypertrophic cardiomyopathy by myocardial contrast echocardiography Heart, October 1, 2007; 93(10): 1204 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Raher, H. Thibault, K. K. Poh, R. Liu, E. F. Halpern, G. Derumeaux, F. Ichinose, W. M. Zapol, K. D. Bloch, M. H. Picard, et al. In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography: Validation and Application in Nitric Oxide Synthase 3 Deficient Mice Circulation, September 11, 2007; 116(11): 1250 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Leong-Poi, M. A. Kuliszewski, M. Lekas, M. Sibbald, K. Teichert-Kuliszewska, A. L. Klibanov, D. J. Stewart, and J. R. Lindner Therapeutic Arteriogenesis by Ultrasound-Mediated VEGF165 Plasmid Gene Delivery to Chronically Ischemic Skeletal Muscle Circ. Res., August 3, 2007; 101(3): 295 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yoshifuku, S. Chen, E. McMahon, J. Korinek, A. Yoshikawa, I. Ochiai, P. P. Sengupta, and M. Belohlavek Parametric Detection and Measurement of Perfusion Defects in Attenuated Contrast Echocardiographic Images J. Ultrasound Med., June 1, 2007; 26(6): 739 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Rakhit, H. Becher, M. Monaghan, P. Nihoyannopoulis, and R. Senior The clinical applications of myocardial contrast echocardiography Eur J Echocardiogr, June 1, 2007; 8(3): s24 - s29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Van Camp, S. Droogmans, and B. Cosyns Bio-effects of ultrasound contrast agents in daily clinical practice: fact or fiction? Eur. Heart J., May 2, 2007; 28(10): 1190 - 1192. [Full Text] [PDF]
|
|
|
|
|
|
L. Galiuto, F. A Gabrielli, A. Lombardo, G. La Torre, A. Scara, A. G Rebuzzi, and F. Crea Reversible microvascular dysfunction coupled with persistent myocardial dysfunction: implications for post-infarct left ventricular remodelling Heart, May 1, 2007; 93(5): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pascotto, K. Wei, A. Micari, T. Bragadeesh, N. Craig Goodman, and S. Kaul Phasic changes in arterial blood volume is influenced by collateral blood flow: implications for the quantification of coronary stenosis at rest Heart, April 1, 2007; 93(4): 438 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Villanueva, E. Lu, S. Bowry, S. Kilic, E. Tom, J. Wang, J. Gretton, J. J. Pacella, and W. R. Wagner Myocardial Ischemic Memory Imaging With Molecular Echocardiography Circulation, January 23, 2007; 115(3): 345 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Geisler, H.C. Rost, P.S. Wild, and R. Zotz Freehand three-dimensional assessment of left ventricular volumes and ejection fraction with ultrasound contrast agent LK565 Eur J Echocardiogr, January 1, 2007; 8(1): 19 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Chantal, J. G. Diodati, J. B. Nasmith, R. Amyot, A. R. LeBlanc, E. Schampaert, and C. Pharand Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2889 - H2896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Dijkmans, R. Senior, H. Becher, T. R. Porter, K. Wei, C. A. Visser, and O. Kamp Myocardial Contrast Echocardiography Evolving as a Clinically Feasible Technique for Accurate, Rapid, and Safe Assessment of Myocardial Perfusion: The Evidence So Far J. Am. Coll. Cardiol., November 8, 2006; (2006) j.jacc.2006.05.079v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Pacella and F. S. Villanueva Effect of Coronary Stenosis on Adjacent Bed Flow Reserve: Assessment of Microvascular Mechanisms Using Myocardial Contrast Echocardiography Circulation, October 31, 2006; 114(18): 1940 - 1947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Pacella, M. V. Kameneva, M. Csikari, E. Lu, and F. S. Villanueva A novel hydrodynamic approach to the treatment of coronary artery disease Eur. Heart J., October 1, 2006; 27(19): 2362 - 2369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Moir, L Hanekom, Z-Y Fang, B Haluska, C Wong, M Burgess, and T H Marwick Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: a study of quantitative contrast echocardiography and strain rate imaging Heart, October 1, 2006; 92(10): 1414 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Okajima, Y Kawase, N Matsushita, S Iwata, A Doi, T Hasegawa, K Hato, M Nishimoto, Y Abe, M Yoshiyama, et al. Usefulness of myocardial contrast echocardiography with nicorandil stress for the detection of coronary artery stenosis. Heart, September 1, 2006; 92(9): 1331 - 1332. [Full Text] [PDF]
|
|
|
|
|
|
A. Micari, M. Pascotto, A. R. Jayaweera, J. Sklenar, N. C. Goodman, and S. Kaul Cyclic variation in ultrasonic myocardial integrated backscatter is due to phasic changes in the number of patent myocardial microvessels. J. Ultrasound Med., August 1, 2006; 25(8): 1009 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van der Laarse and E. E. van der Wall Myocardial contrast echocardiography: another discriminator of physiological and pathological left ventricular hypertrophy? Eur. Heart J., July 1, 2006; 27(13): 1517 - 1518. [Full Text] [PDF]
|
|
|
|
|
|
A. Elhendy and T. R. Porter Myocardial contrast quantitation during stress echocardiography Eur J Echocardiogr, June 1, 2006; 7(3): 185 - 186. [Full Text] [PDF]
|
|
|
|
|
|
E. Toledo, L. D. Jacobs, J. A. Lodato, J. M. DeCara, P. Coon, V. Mor-Avi, and R. M. Lang Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images Eur J Echocardiogr, June 1, 2006; 7(3): 217 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Vincent, L. H. Clerk, J. R. Lindner, W. J. Price, L. A. Jahn, H. Leong-Poi, and E. J. Barrett Mixed meal and light exercise each recruit muscle capillaries in healthy humans Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1191 - E1197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lucidarme, Y. Kono, J. Corbeil, S.-H. Choi, J.-L. Golmard, J. Varner, and R. F. Mattrey Angiogenesis: Noninvasive Quantitative Assessment with Contrast-enhanced Functional US in Murine Model. Radiology, June 1, 2006; 239(3): 730 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Paltiel, L. A. Kalish, R. A. Susaeta, F. Frauscher, P. L. O'Kane, and L. G. Freitas-Filho Pulse-Inversion US Imaging of Testicular Ischemia: Quantitative and Qualitative Analyses in a Rabbit Model Radiology, June 1, 2006; 239(3): 718 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-A. Weber, H. Krakowski-Roosen, S. Delorme, H. Renk, M. Krix, J. Millies, R. Kinscherf, A. Kunkele, H.-U. Kauczor, and W. Hildebrandt Relationship of skeletal muscle perfusion measured by contrast-enhanced ultrasonography to histologic microvascular density. J. Ultrasound Med., May 1, 2006; 25(5): 583 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Perez-David, M A Garcia-Fernandez, J Quiles, P Mahia, J L Lopez-Sendon, E Lopez de Sa, M J Ledesma, M Moreno, M Desco, and E Garcia Usefulness of quantitative myocardial contrast echocardiography for prediction of ventricular function recovery after myocardial infarction treated with primary angioplasty. Heart, May 1, 2006; 92(5): 693 - 694. [Full Text] [PDF]
|
|
|
|
|
|
L. H. Clerk, M. A. Vincent, L. A. Jahn, Z. Liu, J. R. Lindner, and E. J. Barrett Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes, May 1, 2006; 55(5): 1436 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Shohet and P. A. Grayburn Potential Bioeffects of Ultrasonic Destruction of Microbubble Contrast Agents J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1469 - 1470. [Full Text] [PDF]
|
|
|
|
|
|
T. E. Yankeelov, K. J. Niermann, J. Huamani, D. W. Kim, C. C. Quarles, A. C. Fleischer, D. E. Hallahan, R. R. Price, and J. C. Gore Correlation Between Estimates of Tumor Perfusion From Microbubble Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging J. Ultrasound Med., April 1, 2006; 25(4): 487 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bartels and H.-J. Bittermann Transcranial Contrast Imaging of Cerebral Perfusion in Patients With Space-Occupying Intracranial Lesions J. Ultrasound Med., April 1, 2006; 25(4): 499 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Korosoglou, A Hansen, R Bekeredjian, A Filusch, S Hardt, D Wolf, D Schellberg, H A Katus, and H Kuecherer Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies Heart, March 1, 2006; 92(3): 350 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Galiuto, M Lotrionte, F Crea, A Anselmi, G G L Biondi-Zoccai, F De Giorgio, A Baldi, F Baldi, G Possati, M Gaudino, et al. Impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study Heart, February 1, 2006; 92(2): 208 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Toledo, R. M. Lang, K. A. Collins, G. Lammertin, U. Williams, L. Weinert, G. Bolotin, P. D. Coon, J. Raman, L. D. Jacobs, et al. Imaging and Quantification of Myocardial Perfusion Using Real-Time Three-Dimensional Echocardiography J. Am. Coll. Cardiol., January 3, 2006; 47(1): 146 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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., January 3, 2006; 47(1): 65 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vogel, R. Zbinden, A. Indermuhle, S. Windecker, B. Meier, and C. Seiler Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment Eur. Heart J., January 2, 2006; 27(2): 157 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Forsberg, J.-B. Liu, W. T. Shi, R. Ro, K. J. Lipcan, X. Deng, and A. L. Hall In vivo perfusion estimation using subharmonic contrast microbubble signals. J. Ultrasound Med., January 1, 2006; 25(1): 15 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-A. Weber, M. Krix, U. Jappe, H. B. Huttner, M. Hartmann, U. Meyding-Lamade, M. Essig, C. Fiehn, H.-U. Kauczor, and S. Delorme Pathologic Skeletal Muscle Perfusion in Patients with Myositis: Detection with Quantitative Contrast-enhanced US--Initial Results Radiology, December 21, 2005; (2005) 2382041822. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. M. Tsutsui, A. Elhendy, J. R. Anderson, F. Xie, A. C. McGrain, and T. R. Porter Prognostic Value of Dobutamine Stress Myocardial Contrast Perfusion Echocardiography Circulation, September 6, 2005; 112(10): 1444 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Grayburn Stress Echo Without the Stress: Detection of Coronary Stenosis at Rest by Myocardial Contrast Echocardiography Circulation, August 23, 2005; 112(8): 1085 - 1087. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. Leong-Poi, J. Christiansen, P. Heppner, C. W. Lewis, A. L. Klibanov, S. Kaul, and J. R. Lindner Assessment of Endogenous and Therapeutic Arteriogenesis by Contrast Ultrasound Molecular Imaging of Integrin Expression Circulation, June 21, 2005; 111(24): 3248 - 3254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bodi, J. Sanchis, A. Losada, M. P. Lopez-Lereu, D. Garcia, M. Pellicer, F. J. Chorro, and A. Llacer Usefulness of quantitative intravenous myocardial contrast echocardiography to analyze microvasculature perfusion in patients with a recent myocardial infarction and an open infarct-related artery: comparison with intracoronary myocardial contrast echocardiography Eur J Echocardiogr, June 1, 2005; 6(3): 164 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Tsutsui, A. Elhendy, F. Xie, E. L. O'Leary, A. C. McGrain, and T. R. Porter Safety of dobutamine stress real-time myocardial contrast echocardiography J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1235 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Krix, M.-A. Weber, H. Krakowski-Roosen, H. B. Huttner, S. Delorme, H.-U. Kauczor, and W. Hildebrandt Assessment of Skeletal Muscle Perfusion Using Contrast-Enhanced Ultrasonography J. Ultrasound Med., April 1, 2005; 24(4): 431 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Forsberg, W. T. Shi, C. R. B. Merritt, Q. Dai, M. Solcova, and B. B. Goldberg On the Usefulness of the Mechanical Index Displayed on Clinical Ultrasound Scanners for Predicting Contrast Microbubble Destruction J. Ultrasound Med., April 1, 2005; 24(4): 443 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. Bragadeesh, I. Sari, M. Pascotto, A. Micari, S. Kaul, and J. R. Lindner Detection of peripheral vascular stenosis by assessing skeletal muscle flow reserve J. Am. Coll. Cardiol., March 1, 2005; 45(5): 780 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Leong-Poi, M. P. Coggins, J. Sklenar, A. R. Jayaweera, X.-Q. Wang, and S. Kaul Role of collateral blood flow in the apparent disparity between the extent of abnormal wall thickening and perfusion defect size during acute myocardial infarction and demand ischemia J. Am. Coll. Cardiol., February 15, 2005; 45(4): 565 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Miller, H. H. Pien, D. Sahani, A. G. Sorensen, and J. H. Thrall Imaging Angiogenesis: Applications and Potential for Drug Development J Natl Cancer Inst, February 2, 2005; 97(3): 172 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Galiuto Quantifying myocardial perfusion using contrast echocardiography Heart, February 1, 2005; 91(2): 133 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Yamada, K Komuro, T Mikami, N Kudo, H Onozuka, K Goto, S Fujii, K Yamamoto, and A Kitabatake Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography Heart, February 1, 2005; 91(2): 183 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E.R. Weller, M. K.K. Wong, R. A. Modzelewski, E. Lu, A. L. Klibanov, W. R. Wagner, and F. S. Villanueva Ultrasonic Imaging of Tumor Angiogenesis Using Contrast Microbubbles Targeted via the Tumor-Binding Peptide Arginine-Arginine-Leucine Cancer Res., January 15, 2005; 65(2): 533 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H von Bibra, A Hansen, V Dounis, T Bystedt, K Malmberg, and L Ryden Augmented metabolic control improves myocardial diastolic function and perfusion in patients with non-insulin dependent diabetes Heart, December 1, 2004; 90(12): 1483 - 1484. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||