The pulse duration dependence of inertial cavitation dose and hemolysis

Gas-based ultrasound contrast agents increase erythrocyte sonolysis, presumably via enhancing inertial cavitation (IC) activity. The amount of IC activity (IC dose) and hemolysis generated by exposure to 1.15 MHz ultrasound were examined with different ultrasound pulse durations, but with the same delivered acoustic energy for Optison and Albunex. Two types of studies were performed. In the first, bubble generation after each burst of IC activity was quantified using an active cavitation detector, for different pulse durations (5, 10, 20, 30, 50, 100 or 200 cycles), but the same peak-negative pressure (P-) (3 MPa) and total ´on´ time (173.16 ms). Low concentrations of either Optison or Albunex were added into the tank with high-intensity and interrogating transducers orthogonal to each other. For pulse durations >100 cycles, and pulse repetition intervals <5 ms, a ´cascade´ effect (explosive bubble generation) was observed. In the second, IC was measured by passive detection methods. IC dose and hemolysis were determined in whole blood samples at P_=3 MPa and inter-pulse interval (5 ms) which induced the ´cascade´ effect. Each blood sample was mixed with the same number of contrast microbubbles (Optison ∼0.3 v/v % and Albunex ∼0.5 v/v %) but exposed to different pulse durations (5, 10, 20, 30, 50, 100 or 200 cycles). With Optison, up to 60 % hemolysis was produced with long pulses (100 and 200 cycles), compared with <10 % with short pulses (5 and 10 cycles). Albunex generated considerably less IC activity and hemolysis. High pulse repetition frequency (PRF, 500 Hz) generated more hemolysis than the low PRF (200 Hz) at 3 MPa. All experimental results could be explained by the dissolution times of IC-generated bubbles.