ABSTRACT Ultrasound contrast agents provide new opportunities to image vascular volume 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 uniquely combined to aid in the understanding of the effects of transmission parameters and bubble radius on the received echo. These tools allow for optical measurement of radial oscillations of single bubbles during insonation, acoustical study of echoes from single contrast agent bubbles, and the comparison of these experimental observations with theoretical predictions. A modified Herring equation with shell terms is solved for the time-dependent bubble radius and wall velocity, and these outputs are used to formulate the predicted echo from a single encapsulated bubble. The model is validated by direct comparison of the predicted radial oscillations with those measured optically. The transient bubble response is evaluated with a transducer excitation consisting of one-cycle pulses with a center frequency of 2.4-MHz. The experimental and theoretical results are in good agreement and predict 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 pulse with rarefaction first (180°) produces an echo with a mean frequency that is 0.8 MHz higher than the compression-first response (0°), where 0.8 MHz represents a mean over an ensemble of echoes from small (<1.0 μm radius) lipid-shelled bubbles. This shift in the mean frequency decreases with increasing equilibrium radius and is negligible for larger (>1.8 μm radius) bubbles. We have found other significant differences between the echoes from bubbles with a difference in radius of ~0.6 μm. Specifically, for a 2.4 MHz transmitted frequency, larger bubbles (e.g., 1.3 μm radius) produce stronger echoes with a slower ringdown as compared with the smaller bubbles (e.g., 0.7 μm radius). For this transmitted frequency, a radius of 1.4 μm is the calculated linear resonance size.
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