Subharmonic backscattering from ultrasound contrast agents

The ultrasonic contrast of blood in tissue, which is needed for ultrasonic estimation of tissue perfusion, can be increased by injecting the blood wit h bubbles or hollow microspheres. It has been shown that an even greater im provement 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 phys ical parameters of the encapsulated bubble and the threshold pressure is es tablished. The observed increase in the resonance frequency of a coated mic rosphere is explained by introducing the concept of "acoustic radius" of th e encapsulated bubble. It is predicted that subharmonic generation in contr ast agents requires a threshold insonifying pressure, and should be a minim um when microspheres are insonated at twice their resonance frequency. Expe riments confirm the existence of this optimum incident frequency and of a r easonably low threshold pressure for the generation of the subharmonic. The existence of the low threshold pressures for subharmonic generation in con trast agents may prove to be very valuable in ultrasonic contrast imaging. (C) 1999 Acoustical Society of America. [S0001-4966(99)01510-6].