Ultrasonic characterization of ultrasound contrast agents

Abstract

The main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in harmonic energy in the backscattered ultrasound signal, such as energy at the subharmonic, ultraharmonic and higher harmonic frequencies. This harmonic energy is exploited for contrast enhanced imaging to discriminate the contrast agent from surrounding tissue. The amount of harmonic energy that the contrast agent bubbles generate depends on the bubble characteristics in combination with the ultrasound field applied. This paper summarizes different strategies to characterize the UCAs. These strategies can be divided into acoustic and optical methods, which focus on the linear or nonlinear responses of the contrast agent bubbles. In addition, the characteristics of individual bubbles can be determined or the bubbles can be examined when they are part of a population. Recently, especially optical methods have proven their value to study individual bubbles. This paper concludes by showing some examples of optically observed typical behavior of contrast bubbles in ultrasound fields.

Fig. 1

Vibration of a 2.5-μm free bubble and coated bubble (χ = 0.55 N/m and κ_s = 2.3 10⁻⁸ kg/s.) at 2 MHz in water. Top radial oscillation, Middle scattered pressure at 1 cm, Bottom frequency response of scattered pressure

Fig. 2

Attenuation (left) and scatter measurements (right) as function of the frequency

Fig. 3

Harmonic response of Sonovue for four different acoustic pressures (8, 24, 48, 75 kPa). Excitation 3.5 MHz, 10 cycles

Fig. 4

Received scattered power of Quantison by a 10 MHz transducer. The signal was generated by a 1 MHz transducer transmitting an acoustic pressure of 0.3 MPa (dashed) and 0.6 MPa (solid)

Fig. 5

Measured responses of three single bubbles of three different sizes (4.6, 2.1 and 1.5 μm) excited with a driving pressure of 100 kPa. Left panel Measured pressure in Pa. Right Panel frequency response (reproduced with permission of JASA 2008)

Fig. 6

a Sequence of 64 image frames of a 4.2 μm diameter microbubble, driven by a 6-cycle—US burst with a peak negative pressure of 250 kPa. b Diameter–time response. c Power spectrum of diameter–time response

Fig. 7

Bubbles images at 1 MHz and 200 kPa with the Brandaris fast framing camera. Right panel the corresponding D–T curves

Fig. 8

Optical frames showing initial PB127 microbubble (frame 1), shell fissure and gas escape (frames 4, 8–11) under ultrasound of 1.7 MHz, four cycles, MI 1.4 and formation of new free bubbles. Two new free bubbles (frames 41, 47–60) demonstrating oscillations under ultrasound of 1.7 MHz, four cycles and MI 0.25. Last displayed frame shows an optical recording performed 40 ms later, demonstrating bubble disappearance due to dissolution

Fig. 9

Vibration modes