Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz

Inertial cavitation is hypothesized to be a mechanism by which ultrasound ( US) accelerates the dissolution of human blood clots when the clot is expos ed to a thrombolytic agent such as tissue plasminogen activator (t-PA), To test this hypothesis, radiolabeled fibrin clots were exposed or sham-expose d in vitro to 1 MHz c.w. US in a rotating sample holder immersed in a water -filled tank at 37 degreesC, Percent clot dissolution after 60 min of US ex posure was assessed by removing the samples, centrifuging, and measuring th e radioactivity of the supernatant fluid relative to the pelletized materia l, To suppress acoustic cavitation, the exposure tank was contained within a hyperbaric chamber capable of pneumatic pressurization to 10 atmospheres (gauge), Various combinations of static pressure (0, 2, 5, and 7.5 atm gaug e), US (0 or 4 W/cm(2) SATA), and t-PA (0 or 10 mug/mL) were employed, show ing statistically significant reductions in thrombolytic activity as static pressure increased. To gain further insight, an active cavitation detectio n scheme was employed in which 1-mus duration tonebursts of 20-MHz US ( < 1 kPa peak negative pressure, 1 Hz PRF) were used to interrogate clots subje cted to US and static pressure. Results of this cavitation detection scheme showed that scattering from within the clot and broadband acoustic emissio ns that were both present during insonification were significantly reduced with application of static pressure. However, only about half of the accele ration of thrombolysis due to US could be removed by static pressure, sugge sting the possibility of other mechanisms in addition to inertial cavitatio n, (C) 2000 World Federation for Ultrasound in Medicine & Biology.