Nondestructive subharmonic imaging.

Ultrasound contrast agent microbubbles are intravascular agents that can be used to estimate blood perfusion. Blood perfusion may be estimated by destroying the bubbles in a vascular bed and observing the refresh of contrast agents back into the vascular bed. Contrast agents can be readily destroyed by traditional imaging techniques. The design of a nondestructive imaging technique is necessary for the accurate quantification of contrast agent refresh. In this work, subharmonic imaging is investigated as a method for nondestructive imaging with the contrast agent microbubble MP1950 (Mallinckrodt, Inc., St. Louis, MO). Optical observation during insonation, in conjunction with a modified Rayleigh-Plesset (R-P) analysis, provides insight into the mechanisms of and parameters required for subharmonic frequency generation. Subharmonic imaging with a transmission frequency that is the same as the resonant frequency of the bubble is shown to require a minimum pressure of insonation that is greater than the experimentally-observed bubble destruction threshold. Subharmonic imaging with a transmission frequency that is twice the resonant frequency of the bubble produces a subharmonic frequency response while minimizing bubble instability. Optimization is performed using optical experimental analysis and R-P analysis.