| The objective of this study was to investigate the kinetics of contrast agent concentration within the brain when it is subjected to pulsed focused ultrasound. An ultrasound imaging array was mounted within the aperture of a 1.68 MHz focused therapy transducer. Experiments were performed in the brains of rabbits that had undergone craniotomies, with the therapy beam focus localized within one hemisphere. Pulse lengths of 10 ms were employed at repetition rates of 0.1-2 Hz and acoustic powers of 0.1-1 watts. Contrast imaging was performed for up to 9 minutes following the bolus injection of Definity. Contrast signal power was then quantified in regions of interest within the acoustic focus of the therapy beam, as well as in the contra-lateral hemisphere. Following the injection of the contrast agent, signals peaked within 10 seconds and then underwent a period of slow decay. Individual therapy pulses resulted in microbubble depletion within the focus for powers >=0.25W, with full recovery of signal occurring within 1-3 seconds, depending on transmit power. As the pulse repetition rates increased, agent reperfusion between pulses was incomplete and the concentration within the beam was progressively diminished, to a degree dependent upon both power and repetition rates. These results demonstrate that microbubble concentration can be substantially influenced by destruction induced by therapeutic ultrasound pulses. The kinetics of this effect may therefore be a significant factor influencing the efficiency of blood brain barrier breakdown. |