CMUT for ultrafast passive cavitation detection during ultrasound-induced blood-brain barrier disruption: proof of concept study.

ABSTRACT

OBJECTIVE: Cavitation dose monitoring plays a key role in ultrasound drug delivery to the brain. The use of CMUT technology has a great potential for passive cavitation detection (PCD). Approach. Here, a circular (diameter 7mm) capacitive micromachined ultrasonic transducer (CMUT) centered at 5MHz was designed to be inserted into a therapeutic transducer (1.5MHz) used for ultrasound-induced blood-brain barrier (BBB) disruption on mice. CMUT-based real-time cavitation detection was performed during the ultrasound procedure (50µL intravenous injection of SonoVue microbubbles, Frequency 1.5MHz, PNP 480kPa, Duty Cycle 10%, PRF 10Hz, Duration 60s). BBB disruption were confirmed by contrast-enhanced 7T-MRI. Main results. The CMUT device has a fractional bandwidth of 140%, almost twice a conventional piezocomposite PCD transducer. As expected, the CMUT device was able to detect the occurrence of harmonic, subharmonic and ultraharmonic frequencies as well as the increase of broadband signal indicating inertial cavitation in a wide frequency range (from 0.75 to 6 MHz). Signal-to-noise ratio was high enough (> 40 dB) to perform ultrafast monitoring and follow the subtle intrapulse variations of frequency components at a rate of 10 kHz. Significance. This first in vivo proof of concept demonstrates the interest of CMUT for PCD and encourages us to develop devices for PCD in larger animals by integrating an amplifier directly to the CMUT front-end to considerably increase the signal-to-noise ratio.