Experimental and theoretical evaluation of microbubble behavior: Effect oftransmitted phase and bubble size

Ultrasound contrast agents provide new opportunities to image vascular volu me and flow rate directly. To accomplish this goal, new pulse sequences can be developed to detect specifically the presence of a microbubble or group of microbubbles. Here, we consider a new scheme to detect the presence of contrast agents in the body by examining the effect of transmitted phase on the received echoes from single bubbles. In this study, three tools are un iquely combined to aid in the understanding of the effects of transmission parameters and bubble radius on the received echo. These tools allow for op tical measurement of radial oscillations of single bubbles during insonatio n, acoustical study of echoes from single contrast agent bubbles, and the c omparison of these experimental observations with theoretical predictions. A modified Herring equation with shell terms is solved for the time-depende nt bubble radius and wall velocity, and these outputs are used to formulate the predicted echo from a single encapsulated bubble. The model is validat ed by direct comparison of the predicted radial oscillations with those mea sured optically. The transient bubble response is evaluated with a transduc er excitation consisting of one-cycle pulses with a center frequency of 2.4 -MHz. The experimental and theoretical results are in good agreement and pr edict that the transmission of two pulses with opposite polarity will yield similar time domain echoes with the first significant portion of the echo generated when the rarefactional half-cycle reaches the bubble. In addition , both the experimental and theoretical results confirm that the 2.4 MHz pu lse with rarefaction first (180 degrees) produces an echo with a mean frequ ency that is 0.8 MHz higher than the compression-first response (0 degrees) , where 0.8 MHz represents a mean over an ensemble of echoes from small (<1 .0 <mu>m radius) lipid-shelled bubbles. This shift in the mean frequency de creases with increasing equilibrium radius and is negligible for larger (>1 .8 mum radius) bubbles. We have found other significant differences between the echoes from bubbles with a difference in radius of similar to0.6 mum S pecifically, for a 2.4 MHz transmitted frequency, larger bubbles (e.g,, 1.3 mum radius) produce stronger echoes with a slower ring-down as compared wi th the smaller bubbles (e.g., 0.7 mum radius). For this transmitted frequen cy, a radius of 1.4 mum is the calculated linear resonance size.