title: The Effect of Short Duration Ultrasound Pulses on the Interaction Between Individual Microbubbles and Fibrin Clots.
abstract: In previous work, we examined microscale interactions between microbubbles and fibrin clots under exposure to 1 ms ultrasound pulses. This provided direct evidence that microbubbles were capable of deforming clot boundaries and penetrating into clots, while also affecting fluid uptake and inducing fibrin network damage. Here, we investigate the effect of short duration (15 μs) pulses on microscale bubble-clot interactions as function of bubble diameter (3-9 μm) and pressure. Individual microbubbles (n = 45) were placed at the clot boundary with optical tweezers and exposed to 1 MHz ultrasound. High-speed (10 kfps) imaging and 2-photon microscopy were performed during and after exposure, respectively. While broadly similar phenomena were observed as in the 1 ms pulse case (i.e., bubble penetration, network damage and fluid uptake), substantial quantitative differences were present. The pressure threshold for bubble penetration was increased from 0.39 MPa to 0.6 MPa, and those bubbles that did enter clots had reduced penetration depths and were associated with less fibrin network damage and nanobead uptake. This appeared to be due in large part to increased bubble shrinkage relative to the 1 ms pulse case. Stroboscopic imaging was performed on a subset of bubbles (n = 11) and indicated that complex bubble oscillations can occur during this process.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada; Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada. Electronic address: chrisacc@sri.utoronto.ca.
authors.forename: Christopher
authors.initials: C
authors.lastname: Acconcia
authors.affiliation: Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Ben Y C
authors.initials: BY
authors.lastname: Leung
authors.affiliation: Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Anoop
authors.initials: A
authors.lastname: Manjunath
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada; Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: David E
authors.initials: DE
authors.lastname: Goertz
mesh_terms: D001777:Blood Coagulation / Q000502:physiology* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D061185:Mechanical Thrombolysis / Q000379:methods*; D045423:Microbubbles; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D005337:Fibrin
keywords: Contrast agent; Fibrin clot; Microbubbles; Sonothrombolysis; Stroke; Thrombolysis; Ultrasound