Single microbubble acoustics with signal processing: Initial experience with amplitude modulated pulse sequences

The study of acoustic scattering by single microbubbles has the potential to offer improved signal processing techniques. A hydrodynamically focused flow was used In a phantom to Isolate and detect single microbubbles' RF signals using a commercial scanner (Sonos5500, Philips Medical Systems). Two different microbubbles In terms of shell and gas formultation, namely Definity (R) and biSphere (R), are investigated using amplitude modulated pulse sequences. Each microbubble was subjected to a sequence of three 6-cycle amplitude modulated pulses. In each sequence the middle pulse was twice the amplitude of the first and last pulses (half, full half). At 1.62MHz and insonating with low acoustic pressures (full pulse peak negative pressure equal to 180kPa) both agents generally responded proportionally to each of the half, full and half amplitude transmitted pulses. A small percentage of microbubbles (approx. 10%) did not respond to the first half amplitude pulse. At larger amplitudes (full pulse peak negative pressure equal to 550kPa) the majority of microbubbles (approx. 90%) did not produce a measurable echo from the first half amplitude pulse. Mean RMS echo amplitudes at the second harmonic for this dominant population for Definity (R) were 0, 5.5 +/- 3.3, 5.7 +/- 3.5Pascals, and for biSphere (R) 0, 1.1 +/- 0.8, 1.1 +/- 0.9Pascals in response to the 275-550-275kPa sequence. The lack of response to the first 275kPa pulses Is in agreement with previous findings that demonstrate that the number of microbubbles that scatter Increases with acoustic pressure, but may be attributed to different effects for the two agents such as off-resonant size response at the large pressure for Definity (R) and pressure dependant shell damage for biSphere (R). Whilst pulse amplitude modulation is effective in rejecting linear tissue signals and enhancing nonlinear microbubble signals at low acoustic pressures, it does not use the full microbubble signal at larger pressures. More complex pulsing regimes need to be designed to achieve this in the future.