The influence of attachment on the nonlinear behaviour of lipid encapsulated microbubbles at high frequencies

Molecular imaging at higher frequencies (f >;10 MHz) has applications in a preclinical context for a range of disease processes and clinically for the detection of vulnerable atherosclerotic plaques and superficial tumours. The subharmonic response from individual microbubbles in either a bound or unbound state was investigated at both 11 and 25 MHz transmit frequencies. At 11 MHz, unbound bubbles (n=53) were found to have strong subharmonic activity for sizes between 2.4-2.6 μm, while bound (n=50) were most active from 2.6-3.0 μm. Destruction rates were found to differ, with very few unbound bubbles undergoing destruction. At 25 MHz, bound bubble (n=57) activity was found to peak at 1.9 μm as compared to 2.1 μm for the unbound case (n=53), with a 20% increase in amplitude. Comparison with simulations indicates that both unbound and bound bubbles undergo “compression-only” behaviour at 11 MHz, and “expansion-dominated” behaviour at 25 MHz. Subharmonic emissions elicited from 0 radian transmit pulses were found to be p/2 radians out of phase with those elicited from a p radian transmit pulse, suggesting inefficient subharmonic preservation from pulse inversion schemes.