DocumentCode :
770804
Title :
Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification
Author :
Rychak, Joshua J. ; Klibanov, Alexander L. ; Hossack, John A.
Author_Institution :
Virginia Univ., Charlottesville, VA, USA
Volume :
52
Issue :
3
fYear :
2005
fDate :
3/1/2005 12:00:00 AM
Firstpage :
421
Lastpage :
433
Abstract :
Recent research has shown that targeted ultrasound contrast microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that acoustic radiation can be used to force free-stream microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of microbubbles. Lipid microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 /spl times/ 10/sup 6/ to 75 /spl times/ 10/sup 6/ ml/sup -1/. Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s/sup -1/, suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.
Keywords :
adhesion; biomedical ultrasonics; bubbles; capillarity; cardiovascular system; haemodynamics; proteins; ultrasonic transducers; 2.0 MHz; 25 to 122 kPa; P-selectin; acoustic pressure; acoustic radiation force; adhesion enhancement; antibody; clinical dosing range; flow chamber surface; free-stream microbubbles; high-flow vessels; intravascular pathology; lipid microbubbles; microbubble accumulation; microbubble adhesion; microbubble concentration; microbubble delivery; microcapillary flow chamber; target protein; targeted contrast agents; targeted delivery; targeting ligand; transducer; ultrasonic pulse; ultrasound contrast microbubbles; wall shear rate; Adhesives; Cardiac disease; Cardiovascular diseases; In vitro; Injuries; Ischemic pain; Lipidomics; Pathology; Proteins; Ultrasonic imaging; Antibodies; Drug Delivery Systems; Echocardiography; Image Enhancement; Microbubbles; P-Selectin; Ultrasonics;
fLanguage :
English
Journal_Title :
Ultrasonics, Ferroelectrics, and Frequency Control, IEEE Transactions on
Publisher :
ieee
ISSN :
0885-3010
Type :
jour
DOI :
10.1109/TUFFC.2005.1417264
Filename :
1417264
Link To Document :
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