The ultrasound contrast agents increase the ultrasound backscatter and therefore are useful in the enhancement of echogenicity for the assessment of blood flow (Fig. 1). While conventional ultrasound can detect high concentrations of microbubbles, in practice their assessment usually requires contrast-specific imaging modes. Contrast-specific ultrasound modes are generally based on the cancellation and/or separation of linear ultrasound signals from tissue and utilisation of the non-linear response from microbubbles. Non-linear response from microbubbles is based on two different mechanisms: (1) non-linear response from microbubble oscillations at low acoustic pressure, chosen to minimise disruption of the microbubbles, and (2) high-energy broadband non-linear response arising from microbubble disruption.

FIGURE 1. Ultrasound image of a kidney with contrast medium showing absence of perfusion in the upper pole.
Non-linear harmonic ultrasound signals may arise also in tissues themselves due to a distortion of the sound wave during its propagation through the tissue. The extent of this harmonic response from tissue at a given frequency increases with the acoustic pressure, which is proportional to the mechanical index. Low solubility gas ultrasound contrast agents are characterised by the combination of improved stability with favourable resonance behaviour at low acoustic pressure. This allows minimally disruptive contrast-specific imaging at low mechanical index and enables effective investigations over several minutes with the visualisation of the dynamic enhancement pattern in real time. Low mechanical index techniques, furthermore, lead to effective tissue signal suppression, as the non-linear response from the tissue is minimal when low acoustic pressures are used. Ultrasound with air-filled microbubbles at high pressure is dependent on microbubble disruption, which is a significant limitation for real-time imaging.
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