Acoustic lability of albumin microspheres

The sonication of human serum albumin produces air-filled microspheres that are used in echocardiographic studies of myocardial perfusion. Recent studies suggest that the microspheres disappear when high pressures are applied, altering the relationship between the administered microsphere dose and the echocardiographic response. Because an ultrasound pulse generates a pressure wave in insonified medium, we hypothesized that with increasing acoustic pulse pressure, the microsphere concentration decreases, hence ultrasonic backscatter decreases. We measured relative integrated backscatter from albumin microspheres diluted in normal saline solution (6152 microspheres/ml) and 5% human plasma protein fraction (24,608 microspheres/ml), with increasing acoustic pulse pressures at the transducer's focus. Backscatter was also measured in normal saline solution with increasing concentrations (up to 15,380 microspheres/ml) of albumin microspheres at an acoustic pulse pressure of 0.11 MPa (1.1 atm). Backscatter and microsphere concentration were related logarithmically: y = 3.38 x 0.32; r = 0.93. Backscatter was unchanged over time at acoustic pulse (peak compression) pressures less than 0.15 MPa (1.5 atm). However, backscatter decreased readily at acoustic pulse pressures greater than 0.33 MPa (3.3 atm), which included any mixing effects. Thus, albumin microspheres are acoustically labile.