Non-destructive subharmonic imaging

Ultrasound contrast agents provide the ability to estimate microvascular density and flow rate. These small microbubbles can be readily destroyed with sufficient acoustic pressure, typically at a frequency in the low megahertz range. Capillary flow rate may be estimated by destroying the contrast agent in a vascular bed, and estimating the rate of flow of contrast agents back into the vascular bed. In order to accurately assess the flow rate, it is important to monitor the flow without again destroying the contrast agent, and typically a lower acoustic pressure and higher transmitted frequency are required. Subharmonic imaging is investigated here as a method for nondestructive imaging, since a higher transmitted frequency can be employed. Optical observation of the contrast agent during insonation, in conjunction with a modified Rayleigh-Plesset analysis, provides insight into the mechanisms of subharmonic frequency generation. Two operating modes are considered: one in which the transmitted center frequency is equal to the resonance frequency of the bubble; and one in which the transmitted frequency is twice the resonance frequency. A transmission frequency equal to the resonance frequency of the bubble destroys ultrasound contrast agents at pressures too low to produce a subharmonic echo. A transmission frequency that is twice the resonance frequency of the bubble results in a subharmonic echo while minimizing bubble instability.