TY - JOUR
T1 - Efficacy and spatial distribution of ultrasound-mediated clot lysis in the absence of thrombolytics
AU - Ammi, Azzdine Y.
AU - Lindner, Jonathan R.
AU - Zhao, Yan
AU - Porter, Thomas
AU - Siegel, Robert
AU - Kaul, Sanjiv
N1 - Publisher Copyright:
© Schattauer 2015.
PY - 2015
Y1 - 2015
N2 - Ultrasound and microbubble (MB) contrast agents accelerate clot lysis, yet clinical trials have been performed without defining optimal acoustic conditions. Our aim was to assess the effect of acoustic pressure and frequency on the extent and spatial location of clot lysis. Clots from porcine blood were created with a 2-mm central lumen for infusion of lipid-shelled perfluorocarbon MBs (1×107 ml-1) or saline. Therapeutic ultrasound at 0.04, 0.25, 1.05, or 2.00 MHz was delivered at a wide range of peak rarefactional acoustic pressure amplitudes (PRAPAs). Ultrasound was administered over 20 minutes grouped on-off cycles to allow replenishment of MBs. The region of lysis was quantified using contrast-enhanced ultrasound imaging. In the absence of MBs, sonothrombolysis did not occur at any frequency. Sonothrombolysis was also absent in the presence of MBs despite their destruction at 0.04 and 2.00 MHz. It occurred at 0.25 and 1.05 MHz in the presence of MBs for PRAPAs > 1.2 MPa and increased with PRAPA. At 0.25 MHz the clot lysis was located in the far wall. At 1.05 MHz, however, there was a transition from far to near wall as PRAPA was increased. The area of clot lysis measured by ultrasound imaging correlated with that by micro-CT and quantification of debris in the effluent. In conclusion, sonothrombolysis with MBs was most efficient at 0.25 MHz. The spatial location of sonothrombolysis varies with pressure and frequency indicating that the geometric relation between therapeutic probe and vascular thrombosis is an important variable for successful lysis clinically.
AB - Ultrasound and microbubble (MB) contrast agents accelerate clot lysis, yet clinical trials have been performed without defining optimal acoustic conditions. Our aim was to assess the effect of acoustic pressure and frequency on the extent and spatial location of clot lysis. Clots from porcine blood were created with a 2-mm central lumen for infusion of lipid-shelled perfluorocarbon MBs (1×107 ml-1) or saline. Therapeutic ultrasound at 0.04, 0.25, 1.05, or 2.00 MHz was delivered at a wide range of peak rarefactional acoustic pressure amplitudes (PRAPAs). Ultrasound was administered over 20 minutes grouped on-off cycles to allow replenishment of MBs. The region of lysis was quantified using contrast-enhanced ultrasound imaging. In the absence of MBs, sonothrombolysis did not occur at any frequency. Sonothrombolysis was also absent in the presence of MBs despite their destruction at 0.04 and 2.00 MHz. It occurred at 0.25 and 1.05 MHz in the presence of MBs for PRAPAs > 1.2 MPa and increased with PRAPA. At 0.25 MHz the clot lysis was located in the far wall. At 1.05 MHz, however, there was a transition from far to near wall as PRAPA was increased. The area of clot lysis measured by ultrasound imaging correlated with that by micro-CT and quantification of debris in the effluent. In conclusion, sonothrombolysis with MBs was most efficient at 0.25 MHz. The spatial location of sonothrombolysis varies with pressure and frequency indicating that the geometric relation between therapeutic probe and vascular thrombosis is an important variable for successful lysis clinically.
KW - Imaging
KW - Thrombolysis/thrombolytic agents
KW - Ultrasound analysis
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U2 - 10.1160/TH14-03-0286
DO - 10.1160/TH14-03-0286
M3 - Article
C2 - 25809056
AN - SCOPUS:84931275086
SN - 0340-6245
VL - 113
SP - 1357
EP - 1369
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 6
ER -