Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles.
OBJECTIVE
During echo examinations with microbubble contrast, individual "dots" of ultrasound reflection can be visualized. To address the question whether these signals represent individual microbubbles, very dilute suspensions of ultrasound contrast agents or individual microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging.


METHODS
Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin-biotin interaction under microscopy control and subjected to ultrasound imaging.


RESULTS
Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual microbubbles as determined by Coulter. Individual microbubbles immobilized on polystyrene were also visualized by ultrasound.


CONCLUSIONS
Ultrasound medical systems can resolve backscatter signals from individual microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.
Klibanov
Alexander L
AL
University of Virginia Cardiovascular Division, Cardiovascular Imaging Center, Charlottesville, Virginia 22908-0158, USA. alk6n@virginia.edu
Rasche
Peter T
PT
Hughes
Michael S
MS
Wojdyla
Jolette K
JK
Galen
Karen P
KP
Wible
James H
JH
Brandenburger
Gary H
GH
D003287:Contrast Media / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods; D007202:Indicators and Reagents; D008055:Lipids; D045423:Microbubbles; D010713:Phosphatidylcholines; D012680:Sensitivity and Specificity; D012965:Sodium Chloride; D013010:Sonication; D019809:Streptavidin; D014463:Ultrasonography / Q000379:methods*
D003287:Contrast Media; D007202:Indicators and Reagents; D008055:Lipids; D010713:Phosphatidylcholines; D012965:Sodium Chloride; D019809:Streptavidin; C010942:1,2-distearoyllecithin