Noninvasive in vivo cavitation threshold detection during blood-brain barrier opening using focused ultrasound and the contrast agent and definity.

The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) and microbubbles was studied in order to better identify the underlying mechanism. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of definity microbubbles. After definity was injected intravenously, pulsed FUS, with parameters previously shown to generate opening, was applied (frequency: 1.525 MHz, peak-rarefactional pressure: 0.30–0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min) on the right hippocampus of five mice in vivo through their intact skin and skull. T1-weighted MRI was used to verify BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The IC threshold detected was 0.60 MPa and mainly occurred during the first 50 cycles. Harmonics were also detected during BBB opening starting at 0.30 MPa indicating stable cavitation occurrence. In conclusion, stable and inertial cavitation could be detected in vivo without craniotomy and IC is not required for BBB opening. [This work was supported by NIH R21EY018505, NIH R01EB009014 and NSF CAREER 0644713.