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Cardiovascular Applications of Ultrasound Contrast Agents
Table 1: Ultrasound Contrast Agents
Name Manufacturer Shell Gas Diameter (µm) Concentration (ml
-1
) Comments
Levovist Schering None – stabilised Air 1.2 1.2–2·10
8
when Available for cardiological applications
with 0.1% 2.5g is dissolved in 69 countries but not in the US
palmitate in 10ml saline.
Albunex Molecular Biosystems, Denatured human Air 4.3 0.5·10
9
Approved for LV cavity opacification in
Inc. albumin the US, but no longer manufactured
Imagent Alliance Pharamceuticals/ Surfactant-coated Perfluorohexane 5.0 0.5·10
8
Approved for LV cavity opacification in
IMCOR the US, but no longer manufactured
Optison General Electric Denatured human Perflutren 3.0–4.5 5.0–8.0·10
8
Approved for LV cavity opacification
albumin in the US, Europe and Latin America
Sonazoid General Electric Lipid Perflubutane 2.4–2.5 0.3·10
9
Approved in Japan for liver
opacification
Definity Lantheus Medical Imaging Lipid Octafluropropane 1.1–3.3 1.2·10
10
Approved for rest echo LV cavity
opacification in the US, Europe,
Canada, Australia and some
countries in Latin America, Asia and
the Middle East; for radiology
applications in Canada, Mexico and
Australia; and for stress echo in the
EU and Mexico
Sonovue Bracco Diagnostics Lipid Sulphur 2.5 5.0·10
8
Available in Europe for LV cavity
hexafluoride opacification and radiological
applications
Cardio-sphere Point Biomedical, Inc. Bilayer: inner Nitrogen 3.0 2.0–5.0·10
8
Development terminated for
polymer and financial reasons
outer albumin
Imagify Acusphere, Inc. Polymer Decafluorobutane 2.3 Gas is 260±25µg·ml
-1
Under FDA review for myocardial
of reconstituted product perfusion
FDA = US Food and Drug Administration.
stenosis.
88,89
Several studies have reported on the use of CE for the
Figure 9: Contrast-enhanced Images in a Patient with
diagnosis of AMI in the emergency department. In these studies, adding
Tako-Tsubo syndrome
regional function assessment by CE increased the prognostic information of
A B
the clinical variables significantly. When myocardial perfusion assessment is
added, further additional information is obtained. Patients with normal
perfusion and function have excellent outcome, while those in whom both
are abnormal have the worst outcome. Intermediate outcome is noted in
those with normal perfusion despite abnormal function. These patients
include those with spontaneous reperfusion (about one-sixth of the AMI
patients) and those with non-ischaemic cardiomyopathies.
Figure 8 illustrates a large perfusion defect that helped make the diagnosis Contrast-enhanced images showing apical ballooning (arrows in A) in a patient with Tako-Tsubo syndrome who
of AMI in a patient with chest pain and normal electrocardiogram (ECG)
shows normal myocardial perfusion (arrows in B).
(see left panel). This patient had total occlusion of a dominant left
circumflex coronary artery that was opened successfully. A repeat study (see left panel) is captured at the fourth heartbeat after bubble destruction.
showed excellent myocardial reperfusion except in a small apical region If blood flow reserve is normal, the myocardium should replenish within
that showed no reflow (see right panel). A month later there was normal one second at stress, hence the stress image (right panel) is captured at the
wall motion in all myocardial segments except the apex, which continued first heartbeat after bubble destruction. In the normal setting, these two
to show akinesia. Figure 9 illustrates a case of Tako-Tsobu syndrome where images (rest and stress) should look similar. If there is a significant stenosis
apical ballooning (indicated by the arrows) is seen in the B-mode end- in the absence of prior infarction, the rest image should look normal (see
systolic image (see panel A), but myocardial perfusion is normal (see panel left panel in Figure 11), while the stress image should show a defect
B).
91
Based on this study in the emergency department the patient was not (indicated by the arrow in Figure 11).
taken to the catheterisation laboratory and the regional dysfunction
resolved spontaneously. In the absence of prior infarction, the detection of In the presence of infarction, where myocardial blood volume is
CAD on myocardial perfusion imaging is based on the occurrence of markedly reduced due to capillary loss, a fixed defect (present at both
reversible perfusion defects during pharmacological or exercise stress. CE rest and stress) should be noted (indicated by the arrow in Figure 12).
can be used to detect coronary stenosis and to quantify the degree of MBF Similar results are also obtained when dobutamine is used as a stressor.
mismatch during pharmacological stress. Figure 10 demonstrates normal Using this approach, CE had significant incremental value over clinical
perfusion. At rest, microbubble replenishment should occur in four to five factors, resting ejection fraction and wall motion responses in predicting
seconds if blood flow is normal (see Figure 7). Therefore, the rest image events. One of the earliest experimental and clinical applications for CE
ASIA-PACIFIC CARDIOLOGY 45
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