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Polymer-shelled contrast agents demonstrate unique properties because the enclosed gas oscillates freely only after the shell is damaged. We have observed this behavior optically using a high-speed camera, and hypothesize that it leads to the observed acoustical property that the response of a polymer-shelled bubble to a two-pulse sequence depends on the order of pulse transmission. We have observed this property in two different polymer-shelled contrast agents. Based on these findings, we designed a pulse sequence to detect polymer-shelled bubbles, "signal subtraction", in which two same-phase single-cycle pulses are transmitted in succession and the resulting echoes subtracted. This subtraction results in the cancellation of tissue echoes, even in the presence of tissue harmonic generation, with only a small reduction in bubble signal amplitude.