Cavitation microstreaming and stress fields created by microbubbles.

Cavitation microstreaming plays a role in the therapeutic action of microbubbles driven by ultrasound, such as the sonoporative and sonothrombolytic phenomena. Microscopic particle-image velocimetry experiments are presented. Results show that many different microstreaming patterns are possible around a microbubble when it is on a surface, albeit for microbubbles much larger than used in clinical practice. Each pattern is associated with a particular oscillation mode of the bubble, and changing between patterns is achieved by changing the sound frequency. Each microstreaming pattern also generates different shear stress and stretch/compression distributions in the vicinity of a bubble on a wall. Analysis of the micro-PIV results also shows that ultrasound-driven microstreaming flows around bubbles are feasible mechanisms for mixing therapeutic agents into the surrounding blood, as well as assisting sonoporative delivery of molecules across cell membranes. Patterns show significant variations around the bubble, suggesting sonoporation may be either enhanced or inhibited in different zones across a cellular surface. Thus, alternating the patterns may result in improved sonoporation and sonothrombolysis. The clear and reproducible delineation of microstreaming patterns based on driving frequency makes frequency-based pattern alternation a feasible alternative to the clinically less desirable practice of increasing sound pressure for equivalent sonoporative or sonothrombolytic effect. Surface divergence is proposed as a measure relevant to sonoporation.

[1]  Natalia Vykhodtseva,et al.  Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. , 2008, Ultrasonics.

[2]  V. Larrue,et al.  Enhancement of enzymatic fibrinolysis with 2‐MHz ultrasound and microbubbles , 2004, Journal of thrombosis and haemostasis : JTH.

[3]  Theodor Landis,et al.  Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis in acute stroke , 2008, Journal of Thrombosis and Thrombolysis.

[4]  Wesley L. Nyborg,et al.  Small‐Scale Acoustic Streaming in Liquids , 1956 .

[5]  I. Johnsen,et al.  Boundary Layer Flow near a Cylindrical Obstacle in an Oscillating Incompressible Fluid , 1954 .

[6]  J. Polak,et al.  Ultrasound energy and the dissolution of thrombus. , 2004, The New England journal of medicine.

[7]  Junru Wu,et al.  Reparable sonoporation generated by microstreaming. , 2002, The Journal of the Acoustical Society of America.

[8]  Robin H. Liu,et al.  Bubble-induced acoustic micromixing. , 2002, Lab on a chip.

[9]  T. Rink,et al.  Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? , 1987, Nature.

[10]  Richard Manasseh,et al.  Measurement of microbubble-induced acoustic microstreaming using microparticle image velocimetry , 2005, SPIE Micro + Nano Materials, Devices, and Applications.

[11]  A. Ooi,et al.  Time delays in coupled multibubble systems (L) , 2005 .

[12]  Richard Manasseh,et al.  Acoustic microstreaming applied to batch micromixing , 2006, SPIE Micro + Nano Materials, Devices, and Applications.

[13]  Kenneth A. Barbee,et al.  Role of Subcellular Shear–Stress Distributions in Endothelial Cell Mechanotransduction , 2002, Annals of Biomedical Engineering.

[14]  K. Hynynen,et al.  Targeted disruption of the blood–brain barrier with focused ultrasound: association with cavitation activity , 2006, Physics in medicine and biology.

[15]  M. Longuet-Higgins,et al.  Viscous streaming from an oscillating spherical bubble , 1998, Proceedings of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[16]  Stephen Wiggins,et al.  Introduction: mixing in microfluidics , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[17]  Theo Arts,et al.  Wall Shear Stress – an Important Determinant of Endothelial Cell Function and Structure – in the Arterial System in vivo , 2006, Journal of Vascular Research.

[18]  Junru Wu,et al.  Theoretical study on shear stress generated by microstreaming surrounding contrast agents attached to living cells. , 2002, Ultrasound in medicine & biology.

[19]  Ryan L. Steinberg,et al.  Examination of inertial cavitation of Optison in producing sonoporation of chinese hamster ovary cells. , 2008, Ultrasound in medicine & biology.

[20]  S A Small,et al.  Spatio-temporal analysis of molecular delivery through the blood–brain barrier using focused ultrasound , 2007, Physics in medicine and biology.

[21]  K. Hynynen,et al.  Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. , 2008, Ultrasound in medicine & biology.

[22]  Richard Manasseh,et al.  Frequencies of acoustically interacting bubbles , 2009 .

[23]  K. Hynynen,et al.  Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. , 2004, Ultrasound in medicine & biology.

[24]  Richard Manasseh,et al.  Cavitation microstreaming patterns in single and multiple bubble systems , 2007, Journal of Fluid Mechanics.

[25]  K. Hynynen,et al.  Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models , 2008, PloS one.

[26]  M. Fishbein,et al.  Enhancement of thrombolysis in vivo without skin and soft tissue damage by transcutaneous ultrasound. , 1998, Thrombosis research.

[27]  M. S. Chong,et al.  A Description of Eddying Motions and Flow Patterns Using Critical-Point Concepts , 1987 .

[28]  Nico de Jong,et al.  Micromanipulation of endothelial cells: ultrasound-microbubble-cell interaction. , 2004, Ultrasound in medicine & biology.

[29]  S. Illesinghe,et al.  Symmetric mode resonance of bubbles attached to a rigid boundary , 2005 .

[30]  M. V. Dyke,et al.  An Album of Fluid Motion , 1982 .

[31]  Mark Borden,et al.  Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. , 2007, Annual review of biomedical engineering.

[32]  H Sackin,et al.  Mechanosensitive channels. , 1995, Annual review of physiology.

[33]  Stephen Wiggins,et al.  Foundations of chaotic mixing , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[34]  A. Bouakaz,et al.  Characterization of cell membrane response to ultrasound activated microbubbles , 2008, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[35]  E. Unger,et al.  Therapeutic applications of microbubbles , 2001 .

[36]  H. Sackin Review of Mechanosensitive Channels , 1995 .

[37]  Xiaozhou Liu,et al.  Acoustic microstreaming around an isolated encapsulated microbubble. , 2009, The Journal of the Acoustical Society of America.

[38]  M. Longuet-Higgins,et al.  Monopole emission of sound by asymmetric bubble oscillations. Part 2. An initial-value problem , 1989, Journal of Fluid Mechanics.

[39]  A. Bouakaz,et al.  Effect of ultrasound-activated microbubbles on the cell electrophysiological properties. , 2007, Ultrasound in medicine & biology.

[40]  Stephen Meairs,et al.  Ultrasound, microbubbles and the blood-brain barrier. , 2007, Progress in biophysics and molecular biology.

[41]  Win-Li Lin,et al.  Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood-brain-barrier disruption. , 2008, Ultrasonics sonochemistry.

[42]  N Harbeck,et al.  Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Marmottant,et al.  Controlled vesicle deformation and lysis by single oscillating bubbles , 2003, Nature.