Identifying the skull effects to the inertial cavitation threshold of microbubbles in a vessel phantom

The exact mechanism behind the blood-brain barrier (BBB) opening using Focused Ultrasound (FUS) and microbubbles remains unknown. Here, the effects of the murine skull on the pressure threshold of inertial cavitation were investigated using a passive cavitation detector (PCD) in conjunction with B-mode imaging. A cylindrical vessel with a 610-¿m diameter inside a polyacrylamide gel was generated to simulate large blood vessels. Definity^® (Lantheus Medical Imaging, MA, USA) microbubbles with a 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 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 by our 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. Mouse skulls did not affect the pressure threshold of inertial cavitation. The broadband response could be captured through the murine skull, so the same PCD setup can be used in future in vivo applications.