title: In vitro investigations into enhancement of tPA bioavailability in whole blood clots using pulsed-high intensity focused ultrasound exposures.
abstract: Investigations were carried out on the manner by which pulsed-high intensity focused ultrasound (HIFU) enhances the effectiveness of tissue plasminogen activator (tPA) in whole blood clots, in vitro. Scanning electronic microscope (SEM) of the surface of the clots showed that the exposures increased exposed fibrin, as well as the number of openings to more interior regions. These findings were supported by fluorescent antibody labeling of tPA in frozen sections of clots treated post-HIFU. Here, improved accumulation at the surface and penetration of the tPA into the clots were observed in those treated with HIFU. Fluorescence recovery after photobleaching was also performed, indicating that the diffusion coefficient increased 6.3-fold for fluorescently labeled dextrans, comparable in size to tPA, in the HIFU-treated clots. Improved understanding of the manner by which pulsed--HIFU exposures can improve the effectiveness of thrombolytics will help optimize the exposures for this application and potentially facilitate translation to the clinic.
authors.affiliation: Department of Radiology and ImagingSciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Jones
authors.forename: Finnie
authors.initials: F
authors.lastname: Hunter
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Hancock
authors.forename: Ankur
authors.initials: A
authors.lastname: Kapoor
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stone
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: Jianwu
authors.initials: J
authors.lastname: Xie
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Victor
authors.initials: V
authors.lastname: Frenkel
mesh_terms: D001769:Blood / Q000000981:diagnostic imaging; D001777:Blood Coagulation; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014463:Ultrasonography
chemical_list: D010959:Tissue Plasminogen Activator