Nonlinear properties of microbubbles and applications to medical ultrasound imaging

Abstract

Gas bubbles smaller than 10 μm dissolve within milliseconds even in gas-saturated liquids, but coatings, etc. can prevent dissolution. These stabilized microbubbles serve as transpulmonary contrast agents. When only their linear properties are employed, physical laws limit the diagnostic potential to detection in large diameter vessels. Nonlinear acoustic properties of contrast agents permit very important additional applications. Nonlinearity arises from bubble pulsations, shell properties, finite amplitude waves, and electronic hardware. The first two sources can dominate, allowing new diagnostic imaging modes sufficiently sensitive to detect isolated microbubbles in vivo. Harmonic imaging modes detect 2nd harmonics of the transmit frequency, mainly from microbubbles. Acoustic Emission modes destroy bubble shells by one pulse of moderate amplitude. Consequently, the free bubbles respond strongly to this and other pulses before dissolving. Observed lifetimes of 1–20 ms are enough for harmonic or conventional Doppler detection. Typically, bubbles are replenished too slowly to get similar signal intensity for more than one frame at normal rates. Optimal pulse timing should allow new microbubbles to move close to the beam axis before the next pulse arrives. Applications may be counting methods, flow tagging, and quantification of tissue perfusion, possibly combined with single-shot three-dimensional acquisition and HI modes.