Inertial cavitation dose and hemolysis produced in vitro with or without Optison

Gas-based contrast agents (CAs) increase ultrasound (US)-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC dose (ICD) (cumulated root mean squared [RMS] broadband noise amplitude; frequency domain) and 1.1-MHz US-induced hemolysis in whole human blood was explored with Optison®; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: 1. peak negative acoustic pressure (P−), 2. Optison® concentration, 3. pulse duration and 4. total exposure duration and Optison® concentration. P− thresholds for hemolysis and ICD were ∼0.5 MPa. ICD and hemolysis were detected at Optison® concentrations ≥ 0.01 V%, and with pulse durations as low as four or two cycles, respectively. Hemolysis and ICD evolved as functions of time and Optison® concentration; final hemolysis and ICD values depended on initial Optison® concentration, but initial rates of change did not. Within series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p < 0.001. (E-mail: brayman@apl.washington.edu)