Identifying the Inertial Cavitation Pressure Threshold and Skull Effects in a Vessel Phantom Using Focused Ultrasound and Microbubbles

Abstract

Using Focused Ultrasound (FUS) and microbubbles to open the blood‐brain barrier (BBB) has been shown promising for brain drug delivery. However, the exact mechanism behind the opening remains unknown. Here, the effects of the murine skull on the threshold of inertial cavitation were investigated. In order to investigate the pressure threshold for inertial cavitation of preformed microbubbles during sonication, passive cavitation detection in conjunction with B‐mode imaging was used. A cylindrical vessel with a 610‐μm diameter inside a polyacrylamide gel was generated within a polyacrylamide gel to simulate large blood vessels. Definity® (Lantheus Medical Imaging, MA, USA) microbubbles with a 1.1–3.3 μm in diameter at 2.5×107 bubbles/mL were injected into the channel before sonication (frequency: 1.525 MHz; pulse length: 100 cycles; PRF: 10 Hz; sonication duration: 2 s) through an excised mouse skull. A cylindrically focused hydrophone, confocal with the FUS transducer, acted as a passive cavitation detector (PCD) to identify the threshold. A 7.5 MHz linear array with the field‐of‐view perpendicular to the axial length of the FUS beam was also used to image the occurrence of bubble fragmentation. The broadband spectral response acquired at the passive cavitation detector (PCD) and the B‐mode images identified the occurrence and location of the inertial cavitation, respectively. Findings indicated that the peak‐rarefactional pressure threshold was approximately equal to 0.45 MPa at the presence or the absence of the skull. However, the skull induced 10–50% lower inertial cavitation dose. Mouse skulls did not affect the pressure threshold of inertial cavitation but resulted in a lower inertial cavitation dose. The broadband response could be captured through the murine skull, so the same PCD setup can be used in future in vivo applications.