title: Effects of ultrasound frequency and tissue stiffness on the histotripsy intrinsic threshold for cavitation.
abstract: Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Previous work has indicated that a cavitation cloud can be formed by a single pulse with one high-amplitude negative cycle, when the negative pressure amplitude directly exceeds a pressure threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in water-based tissues is determined by the properties of the water inside the tissue, and changes in tissue stiffness or ultrasound frequency will have a minimal impact on the histotripsy intrinsic threshold. To test this hypothesis, the histotripsy intrinsic threshold was investigated both experimentally and theoretically. The probability of cavitation was measured by subjecting tissue phantoms with adjustable mechanical properties and ex vivo tissues to a histotripsy pulse of 1-2 cycles produced by 345-kHz, 500-kHz, 1.5-MHz and 3-MHz histotripsy transducers. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured versus pressure amplitude. The results revealed that the intrinsic threshold (the negative pressure at which probability = 0.5) is independent of stiffness for Young's moduli (E) <1 MPa, with only a small increase (∼2-3 MPa) in the intrinsic threshold for tendon (E = 380 MPa). Additionally, results for all samples revealed only a small increase of ∼2-3 MPa when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold was measured to be between 24.7 and 30.6 MPa for all samples and frequencies tested in this study. Overall, the results of this study indicate that the intrinsic threshold to initiate a histotripsy bubble cloud is not significantly affected by tissue stiffness or ultrasound frequency in the hundreds of kilohertz to megahertz range.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: Evlaisav@umich.edu.
authors.forename: Eli
authors.initials: E
authors.lastname: Vlaisavljevich
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Kuang-Wei
authors.initials: KW
authors.lastname: Lin
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Maxwell
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Warnez
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mancia
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Fowlkes
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Johnsen
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Cain
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D000818:Animals; D002417:Cattle; D055119:Elastic Modulus; D004548:Elasticity; D004867:Equipment Design; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D066298:In Vitro Techniques; D008099:Liver / Q000000981:diagnostic imaging; D008954:Models, Biological; D019047:Phantoms, Imaging; D013710:Tendons / Q000000981:diagnostic imaging; D014059:Tongue / Q000000981:diagnostic imaging; D014463:Ultrasonography; D014867:Water
chemical_list: D014867:Water
keywords: Cavitation; Frequency; Histotripsy; Intrinsic threshold; Tissue mechanical properties