Kaul_edit.qxp 27/2/09 02:49 Page 42
Imaging
Cardiovascular Applications of Ultrasound Contrast Agents
a report by
Sanjiv Kaul
Distinguished Professor of Cardiology, Professor of Medicine and Radiology, and
Head, Division of Cardiovascular Medicine, Oregon Health and Science University
Contrast echocardiography (CE) is 40 years old this year. Gamiak and Shah opacification.
11
Using these approaches, both high MI intermittent imaging
first described the use of ultrasound (US) contrast in 1968 during the early (using B-mode and power Doppler) and low MI continuous imaging are
days of M-mode echocardiography.
1
In that study, US contrast was currently being employed for CE.
produced by inadvertently introducing air bubbles in the indocyanine green
solution that was injected into the left heart during cardiac catheterisation Left Ventricular Cavity Opacification
and observing its appearance in the aortic root. Intravenous injection of The only current US Food and Drug Administration (FDA)-approved
hand-agitated saline that contains small air bubbles has since been used to indication for US contrast agents in the USA is LV endocardial border
detect left-to-right (negative contrast effect in the right atrium) and right- delineation in patients where two or more myocardial segments are not
to-left (appearance of contrast in the left atrium and left ventricle) shunts vizualised on routine echocardiography at rest. The majority of patients
at the inter-atrial level, such as atrial septal defects and patent foramen who benefit from the use of these agents for this specific purpose are those
ovale (see Figure 1). It has also been used to detect pulmonary in intensive care units, those on respirators and those who have poor
arterial–venous malformations and other pulmonary vascular shunts. acoustic windows, such as those with obesity or chronic obstructive
pulmonary disorder. It has been shown that the use of US contrast agents
The bubbles, produced by hand agitation, are relatively large (10–100µm) in such patients provides information identical to the more invasive
and are too short-lived to cross capillary beds, so left ventricular (LV) cavity transoesophageal echocardiography.
15
and myocardial opacification had to wait for the development of small
(smaller than erythrocytes) and stable microbubbles.
2
Currently, there are US contrast agents are also very useful in patients in whom quantitative
many commercially produced US contrast agents (see Table 1) with common assessment of LV ejection fraction is required. It is much easier to trace the
salient features. The microbubbles in these agents do not aggregate, are LV boundaries on end-diastolic and end-systolic still frames when there is
biologically inert and safe,
3,4
remain entirely within the vascular space,
5,6
contrast in the cavity. Figure 2 illustrates four- and two-chamber views
have an intravascular rheology that is similar to that of erythrocytes,
5–7
without and with contrast in the LV cavity: it is clear that despite ‘good’
respond non-linearly to US
8–10
and are eliminated from the body via the images without contrast, LV boundaries can be accurately traced only when
reticuloendothelial system with their gas escaping from the lungs. US contrast is present. Using US contrast provides LV ejection fraction
measurements that are closer to those provided by magnetic resonance
A key technical advance for CE was online signal processing of US imaging.
16
In addition, assessment of LV regional function also becomes
backscatter from insonified microbubbles.
11
Prior to this it was not possible much easier, and less experienced observers can make more accurate
to separate bubble signals from myocardial backscatter without off-line assessments with greater confidence.
17,18
image processing.
12
Unlike tissue, microbubbles are compressible and
oscillate in a US field. At even low mechanical index (MI), these oscillations US contrast agents are also very useful in ruling in or ruling out thrombus in
become non-linear; that is, during each oscillation the microbubbles expand the LV cavity.
19,20
The apex is not always clearly defined in apical views
more than they contract.
13,14
Using novel signal processing techniques the despite the use of harmonic imaging. It is common to mistake the presence
non-linear signals emanating from these oscillating microbubbles can be of LV string or acoustic reverberations for the presence of thrombus,
amplified and the linear signals can be suppressed, resulting in excellent especially if apical wall motion abnormality is also suspected. This obviously
has therapeutic implications, since the presence of thrombus usually
necessitates the use of warfarin, which can have serious side effects.
Sanjiv Kaul is a Distinguished Professor of Cardiology, a
Professor of Medicine and Radiology and Head of the Division
Therefore, accuracy in the definition of thrombus is highly desirable. Figure
of Cardiovascular Medicine at the Oregon Health and Science 3 illustrates the ability of contrast to clearly define the presence of LV
University in Portland. His major clinical and research interest
thrombus, and CE has become the ‘gold standard’ for this purpose. In panel
is coronary artery disease. Dr Kaul has published over 250
papers in the most prestigious cardiovascular journals, and
A there is suggestion of an apical thrombus (identified by the arrow) in a
has been funded continuously by the National Institutes of
non-contrast-enhanced image, while the contrast-enhanced image clearly
Health (NIH) since 1986. He is a member of the American
Society of Clinical Investigation (ASCI), among others, and is
rules out a thrombus. In panel B, use of US contrast clearly demarcates an
on the Editorial Board of the top cardiovascular journals in the world. He is Vice President Elect apical thrombus (identified by the arrow). CE is also used with
of the American Society of Echocardiography (ASE). Dr Kaul received his medical degree from
transoesophageal echocardiography to differentiate left atrial appendage
Delhi University and completed his residency in internal medicine at the University of Vermont.
He completed a two-year clinical cardiology fellowship at the University of California and a
thrombus from ‘smoke’.
21
clinical and research fellowship at the Massachusetts General Hospital, Harvard Medical School.
E: kauls@ohsu.edu
LV cavity masses need not all be thrombi, and CE has been used to
differentiate these masses from thrombi based on their vascularity. Figure 4
42 © TOUCH BRIEFINGS 2008
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