Cardiovascular Applications of Ultrasound Contrast Agents

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Citation
Asia Pacific Cardiology - Volume 2 Issue 1;2008:2(1):42-46

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Contrast echocardiography (CE) is 40 years old this year. Gamiak and Shah first described the use of ultrasound (US) contrast in 1968 during the early days of M-mode echocardiography.1 In that study, US contrast was produced by inadvertently introducing air bubbles in the indocyanine green solution that was injected into the left heart during cardiac catheterisation and observing its appearance in the aortic root. Intravenous injection of hand-agitated saline that contains small air bubbles has since been used to detect left-to-right (negative contrast effect in the right atrium) and right-to- left (appearance of contrast in the left atrium and left ventricle) shunts at the inter-atrial level, such as atrial septal defects and patent foramen ovale (see Figure 1). It has also been used to detect pulmonary arterial–venous malformations and other pulmonary vascular shunts.
The bubbles, produced by hand agitation, are relatively large (10–100μm) and are too short-lived to cross capillary beds, so left ventricular (LV) cavity and myocardial opacification had to wait for the development of small (smaller than erythrocytes) and stable microbubbles.2 Currently, there are many commercially produced US contrast agents (see Table 1) with common salient features. The microbubbles in these agents do not aggregate, are biologically inert and safe,3,4 remain entirely within the vascular space,5,6 have an intravascular rheology that is similar to that of erythrocytes,5–7 respond non-linearly to US8–10 and are eliminated from the body via the reticuloendothelial system with their gas escaping from the lungs.
A key technical advance for CE was online signal processing of US backscatter from insonified microbubbles.11 Prior to this it was not possible to separate bubble signals from myocardial backscatter without off-line image processing.12 Unlike tissue, microbubbles are compressible and oscillate in a US field. At even low mechanical index (MI), these oscillations become non-linear; that is, during each oscillation the microbubbles expand more than they contract.13,14 Using novel signal processing techniques the non-linear signals emanating from these oscillating microbubbles can be amplified and the linear signals can be suppressed, resulting in excellent opacification.11 Using these approaches, both high MI intermittent imaging (using B-mode and power Doppler) and low MI continuous imaging are currently being employed for CE.

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