Pressure dependence of subharmonic signals from contrast microbubbles

Noninvasive pressure estimation in heart cavities and in major vessels would provide clinicians with a valuable tool for assessing patients with heart and vascular diseases. Some microbubble-based ultrasound contrast agents are particularly well suited for pressure measurements because their substantial compressibility enables microbubbles to vary significantly in size in response to changes in pressure. Pressure changes should then affect reflectivity of microbubbles after intravenous injection of a contrast agent. This has been demonstrated with a galactose-based contrast agent using 2.0-MHz ultrasound tone bursts. Preliminary results indicate that, over the pressure range of 0-186 mmHg, the subharmonic amplitude of scattered signals decreases by as much as 10 dB under optimal acoustic settings and the first and second harmonic amplitudes decrease by less than 3 dB. An excellent correlation between the subharmonic amplitude and the hydrostatic pressure suggests that the subharmonic signal may be utilized for noninvasive detection of pressure changes.