Bednarz, James E

DeCara, Jeanne M

Kirkpatrick, James N

Lang, Roberto M

Spencer, Kirk T

Ward, R.Parker

Elsevier - Publisher Connector 

881-5 Comparison of modified acoustic quantification with echocardiographic contrast and radionuclide ventriculography for evaluation of left ventricular ejection fraction 

374A ABSTRACTS - Noninvasive Imaging JACC March 3, 2004
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of QCA or clinical data. A coronary stenosis >70% was considered significant. Results.
Fourteen patients had no significant disease at QCA, 12 had one vessel, and three had
multi-vessel disease. In the 15 patients with disease, 10 were detected by MP at peak
stress, 8 were detected by WM with CEBD, and 6 were detected by WM without contrast.
MP abnormalities in CAT supplied by >70% diameter stenosis were seen in an additional
nine CAT by R1 and four CAT by R2 that were considered to have normal WM with or
without CEBD. MP abnormalities were seen during the intermediate stage of the DSE in
9 of the 10 patients with disease at QCA and abnormal MP at peak stress. Conclusions.
These pilot data indicate that the addition of RTLMII following IV contrast during DSE
improves test sensitivity because it detects MP abnormalities that occur in CAT with nor-
mal WM even with CEBD.
11:00 a.m.
881-3 Real-Time Contrast Enhanced Ultrasound Imaging of 
Neovascularization Within the Human Carotid Plaque
Rachel Neems, Matt Feinstein, Marshall Goldin, John Dainauskas, Paul Espinoza, 
Mahala Johnson, Maria Daniels, Philip R. Liebson, James E. Macioch, Steven B. 
Feinstein, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL
Objective: 1) To review contrast-enhanced ultrasound studies of human carotid artery
atherosclerosis to determine incidence of plaque neovascularization, 2) to correlate
neovascularization observed during non-invasive imaging to pathologic specimens.
Background: Previous pathologic studies have shown that neovascularization within the
human atherosclerotic plaque revealed a far greater incidence of neovascularization from
the adventitia relative to the lumen and a correlation between plaque instability and
carotid occlusive disease.
Methods:Twenty-one contrast-enhanced carotid examinations were reviewed (criteria for
review >50% stenosis). The degree of neovascularization was visually graded.
Results: Neovascularization by contrast-enhanced ultrasound imaging was observed in
the carotid artery plaque in 20/21 patients. Four (4) were considered to be extensive;
moderate in 5; and minimal in 11 patients. The histology specimens in 2 patients follow-
ing endarectomy revealed degrees of plaque neovascularization consistent with the
images obtained with contrast-enhanced ultrasound imaging. 
Conclusion: This is the first report of real-time, contrast-enhanced, ultrasound imaging of
the neovascularization within the human carotid plaque. Neovascularization was
observed in 95% (20/21) of the carotid images and associated with a perfusion pattern
described as "outside-in" (originating in the adventitia and leading to the intima).
11:15 a.m.
881-4 Delivery of Luciferase Enzyme to the Heart Using 
Ultrasound Targeted Microbubble Destruction
Raffi Bekeredjian, Shuyuan Chen, Paul A. Grayburn, Ralph V. Shohet, University of 
Texas Southwestern Medical Center, Dallas, TX, Baylor Heart and Vascular Institute, 
Dallas, TX
Background: We have previously shown that ultrasound targeted microbubble destruc-
tion (UTMD) can direct plasmids to the heart. Other groups have been using this or simi-
lar techniques to deliver proteins or drugs to ultrasound accessible organs. The aim of
this study was to evaluate UTMD for protein and drug delivery with lipid stabilized
microbubbles (MB) using luciferase enzyme as a highly specific and sensitive reporter for
quantification.
Methods: 1 µg of luciferase protein was added before assembly of lipid stabilized
microbubbles. Microbubbles were infused intravenously over 15 minutes into three rats
and high mechanical index ultrasound was applied to destroy intramyocardial microbub-
bles. Three rats receiving 1 µg of luciferase protein in PBS with ultrasound served as a
control. Heart, lung, liver and skeletal muscle were harvested immediately after the
experiment and relative luminescence units (RLU) per mg protein per second was deter-
mined.
Results: In the microbubble group hearts showed 6-fold augmented luciferase activity
compared to the control (751000 vs. 119000 RLU/mg protein/s; p=0.014). The other
organs showed comparable activity between these groups.Conclusion: This study
shows that lipid stabilized microbubbles can be used to deliver proteins to the heart. The
6-fold augmentation of protein uptake in the hearts compares with no change in the
uptake of other organs between the groups. This serves as a model for directing proteins
and drugs to ultrasound accessible organs using UTMD.
11:30 a.m.
881-5 Comparison of Modified Acoustic Quantification With 
Echocardiographic Contrast and Radionuclide 
Ventriculography for Evaluation of Left Ventricular 
Ejection Fraction
James N. Kirkpatrick, R. Parker Ward, Roberto M. Lang, James E. Bednarz, Jeanne M. 
DeCara, Kirk T. Spencer, University of Chicago, Chicago, IL
Background. Determination of left ventricular ejection fraction (LVEF) provides one of
the most powerful prognostic assessments in cardiovascular medicine.Radionuclide ven-
triculography (RNV) is considered the gold standard for determination of LVEF because it
is quantitative and accurate. However, it is expensive and involves cumbersome prepara-
tion and care of radiopharmaceuticals. When combined with echocardiographic contrast
infusion, modified acoustic quantification (AQ) can provide real-time quantitative assess-
ment of LVEF, even in patients with poor acoustic windows. We sought to compare the
quantitative measurements of LVEF obtained from contrast AQ with LVEF measurements
from RNV. Methods. Thirty-nine patients scheduled for RNV for assessment of LVEF
were recruited. After their nuclear study, patients underwent echocardiographic determi-
nation of LVEF using acoustic quantification with a continuous infusion of Definity® con-
trast agent (Bristol-Meyers Squibb) in apical four chamber (A4C) and apical two chamber
(A2C) views. Ultrasound settings were optimized to track the endocardial border. LV vol-
ume curves from each cardiac cycle were averaged to form a real-time composite wave-
form, from which LVEF was calculated. Contrast was titrated to provide optimal
opacification of the LV cavity. Results. Contrast infusion resulted in uniform LV opacifica-
tion, allowing accurate endocardial border detection and tracking throughout the cardiac
cycle in 38 patients (97%). The mean LVEF by RNV was 50±16% (range, 19-73%). The
average LVEF by acoustic quantification with contrast was 49±17% for A4C and 51±18%
for A2C. The average difference between LVEF by RNV and LVEF by the mean of A4C
and A2C was <1%. Conclusion. Echocardiography using acoustic quantification with
contrast for quantitative determination of LVEF compared favorably with radionuclide ven-
triculography. This novel technique shows promise as a relatively inexpensive and easy
method for quantitative assessment of LVEF.
11:45 a.m.
881-6 Effect of Attenuation on Intravascular Thrombus 
Dissolution Using Transcutaneous Ultrasound and 
Intravenous Microbubbles
Thomas R. Porter, Jeane Mike Tsutsui, Jason M. Johanning, B. Timothy Baxter, John 
Lof, Terry Matsunaga, Reena Zutshi, Evan Unger, Feng Xie, University of Nebraska 
Medical Center, Omaha, NE
Although low frequency ultrasound (LFUS) and intravenous (IV) microbubbles (MB) have
been used to recanalize arterial thromboses, the effect of ultrasound attenuation (ATT)
has not been assessed. We hypothesized that higher intensity LFUS would attenuate
more than lower intensities (I), resulting in lower effectiveness. To test this, chronic arteri-
ovenous grafts were repeatedly thrombosed in 3 dogs. One megahertz LFUS at different
I and duty cycles (DC) was applied transcutaneously in the presence and absence of a 6
cm thick tissue mimicking phantom (ATT coefficient: 0.49dB/cm/MHz). The different I and
DC used were 0.4 Watts/cm2 continuous wave (0.4 CW), 0.8 Watts/cm2 CW (0.8 CW),
and 10 W/cm2 pulsed wave at 10% DC (10 PW). IV lipid MB (0.1-0.2 ml bolus) or saline
were administered at 3-5 minute intervals during LFUS application. Angiographic reflow
(AR) was assessed at 30 and 45 minutes of treatment. Patency score (PS) in each limb
of the graft (proximal, mid, and distal) was defined as 0=100% occluded, 1=>10%,
2=>30%, 3=>70%, and 4=>90% recanalized. Results. A total of 45 thrombosed grafts
were tested (mean age of thrombus 3.8±0.9 hours). In the presence of the phantom, AR
in the graft was faster and PS was higher with 0.4 CW LFUS (Table). The PS for 10 PW
was significantly lower in the presence of the phantom (Table). Conclusions. These find-
ings indicate that LFUS at lower I should be used to recanalize thrombosed vessels
where significant ATT is present, such as in acute coronary and cerebral thromboses.
Plaque neo-vascularization
Patients Statin No Statin Unknown
MI
(Average)
Limited 11 5 3 3 0.12
Moderate 5 2 -- 3 0.14
Extensive 4 1 2 1 0.09
None 1 -- -- 11
Totals 21 8 5 7


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881-5 Comparison of modified acoustic quantification with echocardiographic contrast and radionuclide ventriculography for evaluation of left ventricular ejection fraction

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