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The ultrasonic contrast of blood in tissue, which is needed for ultrasonic estimation of tissue perfusion, can be increased by injecting the blood with bubbles or hollow microspheres. It has been shown that an even greater improvement in contrast can be obtained by using the subharmonic generated by irradiated microspheres. By obtaining analytical solutions to the modified RPNNP equation for a coated microbubble, the relationship between the physical parameters of the encapsulated bubble and the threshold pressure is established. The observed increase in the resonance frequency of a coated microsphere is explained by introducing the concept of "acoustic radius" of the encapsulated bubble. It is predicted that subharmonic generation in contrast agents requires a threshold insonifying pressure, and should be a minimum when microspheres are insonated at twice their resonance frequency. Experiments confirm the existence of this optimum incident frequency and of a reasonably low threshold pressure for the generation of the subharmonic. The existence of the low threshold pressures for subharmonic generation in contrast agents may prove to be very valuable in ultrasonic contrast imaging.

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A double frequency method of measuring bubble size which has better spatial resolution than previous techniques, is described. Bubbles are insonified simultaneously by a swept, relatively low, ‘‘pumping’’ frequency near their resonance and a high ‘‘imaging’’ frequency. Theoretical expressions are derived for the sound scattered by a bubble under the influence of these two frequencies. Existence of sharp resonance behavior in the scattered sound at the sum frequency is shown both theoretically and experimentally.

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