Broadband noise emissions produced by pulsed 1-MHz ultrasound exposures in the presence or absence of Optison, and their relationship to the hemolytic bioeffect

Abstract

Gas-based contrast agents are known to increase ultrasound-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC ‘‘dose’’ (ICD) (cumulated rms broadband noise amplitude in the frequency domain) and 1.1-MHz ultrasound-induced hemolysis in whole human blood was explored with additions of Optison or degassed saline; 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 variable Optison concentration. The P– thresholds for hemolysis and ICD above noise levels were ∼0.5 MPa. Enhancement of ICD and hemolysis was detected even at the lowest Optison concentration tested (0.1%) at P−=3 MPa. At 2 MPa P–(0.3% Optison), significant hemolysis and ICD were detected with pulse durations as brief as 2 and 4 cycles, respectively. At 3 MPa P–, hemolysis and ICD evolved as functions of time and Optison concentration; ultimate levels of hemolysis and ICD depended strongly on initial Optison concentration, but initial rates of change did not. Within experimental series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p less than 0.001.