In vitro evaluation of ultrasound-assisted thrombolysis using a targeted ultrasound contrast agent.
A thrombus-targeted ultrasound contrast agent bound with tirofiban - a glycoprotein (GP) IIb/IIIa antagonist that can specifically bind to activated platelets in the thrombus - was designed to enhance both the image contrast and thrombolysis effect. In this study, we used 76 canine thrombi for investigation. The targeting ability to thrombi was confirmed by microphotography and high-frequency ultrasound (40 MHz) imaging. The effect of the targeted microbubbles on thrombolysis enhancement was investigated using an in vitro flow system: targeted and nontargeted microbubbles flowed through the clot for 30 seconds with a washing step; the microbubbles remained on the clot that were then cavitated by ultrasound (frequency = 1 MHz, MI = 1.2). The extent of thrombolysis was evaluated by weight reduction and histology analysis. The targeted microbubbles reduced the weight of thrombi by a factor of 1.7 times that of the nontargeted microbubbles. (clot weight reduction: 23.1 +/- 5.3% versus 13.6 +/- 4.9%, p < 0.01 between targeted and nontargeted group), and the signal enhancement was 3.34 +/- 0.30 dB (mean +/- SD, p < 0.01 compared to control). We conclude that targeted microbubbles are applicable not only for molecular imaging of thrombi but also for improving the effectiveness of ultrasound-assisted thrombolysis.
Chen
Szu-Chia
SC
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Ruan
Jia-Ling
JL
Cheng
Po-Wen
PW
Chuang
Yueh-Hsun
YH
Li
Pai-Chi
PC
D000818:Animals; D015415:Biomarkers; D003287:Contrast Media; D004285:Dogs; D005343:Fibrinolytic Agents; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D045423:Microbubbles; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D012709:Serum Albumin; D012965:Sodium Chloride; D013010:Sonication / Q000379:methods*; D015912:Thrombolytic Therapy / Q000379:methods*; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives*; D014465:Ultrasonics; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000000981:diagnostic imaging*
D015415:Biomarkers; D003287:Contrast Media; D005343:Fibrinolytic Agents; D012709:Serum Albumin; D014443:Tyrosine; D012965:Sodium Chloride; D000077466:Tirofiban