Objective. The purpose of this study was to identify the pressure threshold for the destruction of Optison (octafluoropropane contrast agent; Amersham Heakh, Princeton, NJ) using a laboratory-assembled 3.5-MHz pulsed ultrasound system and a clinical diagnostic ultrasound scanner Methods. A 3.5-MHz focused transducer and a linear array with a center frequency of 6.9 MHz were positioned confocally and at 90 degrees to each other in a tank of deionized water Suspensions of Optison (5-8 x 10(4) microbubbles/mL) were insonated with 2-cycle pulses from the 3.5-MHz transducer (peak rarefactional pressure, or P-r, from 0.0, or inactive, to 0.6 MPa) while being interrogated with fundamental B-mode imaging pulses (mechanical index, or MI, = 0.04). Scattering received by the 3.5-MHz transducer or the linear array was quantified as mean backscattered intensity or mean digital intensity, respectively, and fit with exponential decay functions (Ae(-kt) + N, where A + N was the amplitude at time 0, N, background echogenicity; and k, decay constant). By analyzing the decay constants statistically, a pressure threshold for Optison destruction due to acoustically driven diffusion was identified. Results. The decay constants determined from quantified 3.5-MHz radio frequency data and B-mode images were in good agreement. The peak rarefactional pressure threshold for Optison destruction due to acoustically driven diffusion at 3.5 MHz was 0.15 MPa (MI = 0.08). Furthermore, the rate of Optison destruction increased with increasing 3.5-MHz exposure pressure output. Conclusions. Optison destruction was quantified with a laboratory-assembled 3.5-MHz ultrasound system and a clinical diagnostic ultrasound scanner. The pressure threshold for acoustically driven diffusion was identified, and 3 distinct mechanisms of ultrasound contrast agent destruction were observed with acoustic techniques.