title: Identifying the inertial cavitation threshold and skull effects in a vessel phantom using focused ultrasound and microbubbles.
abstract: Focused ultrasound (FUS) in combination with microbubbles has been shown capable of delivering large molecules to the brain parenchyma through opening of the blood-brain barrier (BBB). However, the mechanism behind the opening remains unknown. 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 cerebral vessel was simulated by generating a cylindrical hole of 610 microm in diameter inside a polyacrylamide gel and saturating its volume with microbubbles. Definity microbubbles (Mean diameter range: 1.1-3.3 microm, Lantheus Medical Imaging, N. Billerica, MA, USA) were injected prior to sonication (frequency: 1.525 MHz; pulse length: 100 cycles; PRF: 10 Hz; sonication duration: 2 s) through an excised mouse skull. The acoustic emissions due to the cavitation response were passively detected using a cylindrically focused hydrophone, confocal with the FUS transducer and a linear-array transducer with the field of view perpendicular to the FUS beam. 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, with or without the skull present. Mouse skulls did not affect the 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 set-up can be used in future in vivo applications.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA.
authors.forename: Yao-Sheng
authors.initials: YS
authors.lastname: Tung
authors.forename: James J
authors.initials: JJ
authors.lastname: Choi
authors.forename: Babak
authors.initials: B
authors.lastname: Baseri
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Konofagou
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000528:radiation effects*; D005740:Gases / Q000737:chemistry* / Q000528:radiation effects*; D051379:Mice; D045423:Microbubbles; D019047:Phantoms, Imaging; D011829:Radiation Dosage; D012886:Skull / Q000502:physiology* / Q000528:radiation effects*; D013010:Sonication
chemical_list: D003287:Contrast Media; D005740:Gases