title: Dynamics of targeted microbubble adhesion under pulsatile compared with steady flow.
abstract: Hemodynamic flow variations at low fluid shear stress are thought to play a critical role in local atherosclerotic plaque initiation and development and to affect plaque instability. Targeted microbubbles are being developed as intravascular agents for identifying atherosclerotic lesions using ultrasound. How variations in local hydrodynamic flow influence the adhesiveness of targeted microbubbles is not well understood. We postulated that rates of targeted microbubble binding and accumulation differ when subjected to steady flow (SF) as compared with oscillatory or pulsatile flow (PF), because PF imposes non-uniform blood rheology and periodic acceleration and deceleration of blood velocity, when compared with SF. We assessed the binding rates of targeted microbubbles in seven randomly assigned PF and seven matched SF replicate runs at low (<1 Pa) and intermediate (≥1 and <2.5 Pa) wall shear stress (WSS) by drawing 4.8 × 10(6) microbubbles mL(-1) over streptavidin-coated substrates, immobilized within a parallel plate flow chamber at a calculated density of 81 binding sites μm(-2). Selective binding and accumulation of targeted microbubbles was recorded in a single field of view using real-time video microscopy. Microbubble accumulation was modeled to obtain flow-mediated microbubble binding kinetics (amplitude, A, and rate constant, k). PF elicited higher microbubble accumulation rates, in comparison to SF. The rates of microbubble accumulation differed significantly between PF and SF (p < 0.05) at intermediate WSS but not at low WSS (p > 0.05). The rate of microbubble accumulation decreased as WSS increased.
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom; Imaging Sciences Department, Imperial College London, London, United Kingdom. Electronic address: c.sennoga@imperial.ac.uk.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sennoga
authors.affiliation: Department of Chemistry, Imperial College London, London, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Seddon
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Frueh
authors.affiliation: Key Laboratory of Modern Acoustics of Ministry of Education, Institute of Acoustics, Nanjing University, Nanjing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Dorian O
authors.initials: DO
authors.lastname: Haskard
authors.affiliation: Division of Imaging Sciences, Biomedical Engineering Department, King's College London, London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Eckersley
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom.
authors.forename: Meng-Xing
authors.initials: MX
authors.lastname: Tang
mesh_terms: D001161:Arteriosclerosis / Q000000981:diagnostic imaging; D002138:Calibration; D004867:Equipment Design; D045423:Microbubbles; D018715:Microscopy, Video; D011673:Pulsatile Flow; D012212:Rheology; D019809:Streptavidin; D013314:Stress, Mechanical; D013499:Surface Properties; D018617:Ultrasonography, Doppler, Pulsed
chemical_list: D019809:Streptavidin
keywords: Molecular imaging; Pulsatile flow; Steady flow; Targeted microbubbles; Wall shear stress