title: Quantitative guidelines for the prediction of ultrasound contrast agent destruction during injection.
abstract: Experiments and theory were undertaken on the destruction of ultrasound contrast agent microbubbles on needle injection, with the aim of predicting agent loss during in vivo studies. Agents were expelled through a variety of syringe and needle combinations, subjecting the microbubbles to a range of pressure drops. Imaging of the bubbles identified cases where bubbles were destroyed and the extent of destruction. Fluid-dynamic calculations determined the pressure drop for each syringe and needle combination. It was found that agent destruction occurred at a critical pressure drop that depended only on the type of microbubble. Protein-shelled microbubbles (sonicated bovine serum albumin) were virtually all destroyed above their critical pressure drop of 109 ± 7 kPa Two types of lipid-shelled microbubbles were found to have a pressure drop threshold above which more than 50% of the microbubbles were destroyed. The commercial lipid-shelled agent Definity was found to have a critical pressure drop for destruction of 230 ± 10 kPa; for a previously published lipid-shelled agent, this value was 150 ± 40 kPa. It is recommended that attention to the predictions of a simple formula could preclude unnecessary destruction of microbubble contrast agent during in vivo injections. This approach may also preclude undesirable release of drug or gene payloads in targeted microbubble therapies. Example values of appropriate injection rates for various agents and conditions are given.
authors.affiliation: CSIRO Materials Science and Engineering, Highett, Melbourne, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Threlfall
authors.forename: Hong Juan
authors.initials: HJ
authors.lastname: Wu
authors.forename: Katherine
authors.initials: K
authors.lastname: Li
authors.forename: Ben
authors.initials: B
authors.lastname: Aldham
authors.forename: Judith
authors.initials: J
authors.lastname: Scoble
authors.forename: Ilija D
authors.initials: ID
authors.lastname: Sutalo
authors.forename: Anna
authors.initials: A
authors.lastname: Raicevic
authors.forename: Luisa
authors.initials: L
authors.lastname: Pontes-Braz
authors.forename: Brian
authors.initials: B
authors.lastname: Lee
authors.forename: Michal
authors.initials: M
authors.lastname: Schneider-Kolsky
authors.forename: Andrew
authors.initials: A
authors.lastname: Ooi
authors.forename: Greg
authors.initials: G
authors.lastname: Coia
authors.forename: Richard
authors.initials: R
authors.lastname: Manasseh
mesh_terms: D000418:Albumins / Q000737:chemistry* / Q000528:radiation effects / Q000592:standards*; D001315:Australia; D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects / Q000592:standards; D004353:Drug Evaluation, Preclinical / Q000592:standards; D004355:Drug Stability; D017408:Guidelines as Topic; D007267:Injections / Q000295:instrumentation / Q000379:methods*; D011312:Pressure; D014463:Ultrasonography / Q000379:methods* / Q000592:standards*
chemical_list: D000418:Albumins; C060687:Albunex; D003287:Contrast Media
keywords: Destruction; Injection; Microbubbles; Pressure drop; Ultrasound contrast agent