Michael Joseph Stone BS, Presenter: Nothing to Disclose

Victor Frenkel PhD, Abstract Co-Author: Nothing to Disclose

Jay Oberoi, Abstract Co-Author: Nothing to Disclose

Bradford Wood MD, Abstract Co-Author: Nothing to Disclose

McDonald Horne MD, Abstract Co-Author: Nothing to Disclose

King Chuen Peter Li MD, Abstract Co-Author: Nothing to Disclose

Pulsed-HIFU exposures have been found to enhance the delivery of various substances in vivo. The purpose of this study was to investigate the enhancing effects of pulsed-HIFU exposures on tPA mediated thrombolysis, and to elucidate the mechanisms of this action.

Clots were formed by placing 1 mL of blood from human volunteers in sections of penrose tubing in 37° water bath for 90 minutes. Real or sham pulsed-HIFU exposures (1 MHz, 10% duty cycle, 60 watts, 60 pulses per exposure site) were followed by incubations in t-PA (in saline) or saline only. To evaluate enhanced thrombolysis, 4 experimental groups (control, HIFU only, t-PA only, HIFU + t-PA) were evaluated. Thrombolysis was measured as the relative reduction in the mass of the clot. D-dimer assays were also performed. Clots were visualized by scanning electron microscopy. Clot penetration of tPA was evaluated by incubating clots in a tPA solution followed by fixation and staining with fluorophore-labeled monoclonal antibodies to tPA. Ultrasound RF data was collected before and after individual pulses in order to visualize the displacements produced in the clots by the exposures.

Clots treated with pulsed-HIFU alone did not show significant increases in thrombolysis when compared to controls. A 51% increase in thrombolysis for HIFU + t-PA treated clots was seen compared to those treated with t-PA only; these results were further corroborated by the D-dimer levels. Scanning electron micrographs showed the surface of treated clots to be more porous when compared to controls. These results were supported by the fluorescent antibody labeling, where improved penetration and overall binding was found in the pulsed-HIFU treated clots. Displacements produced in the clots as a result of the exposures were on the order of 100 to 200 μm.

Results of the study showed that the pulsed-HIFU exposures significantly enhanced tPA mediated thrombolysis in a novel in vitro model. It is hypothesized that the displacements produced by the exposures created structural changes in the surface of the clots allowing for increased penetration and binding of t-PA, and consequently improved rates of thrombolysis.

Stone, M, Frenkel, V, Oberoi, J, Wood, B, Horne, M, Li, K, Pulsed-High Intensity Focused Ultrasound (HIFU)-enhanced Thrombolysis in Vitro: Proof of Concept and Investigation of Mechanism.  Radiological Society of North America 2005 Scientific Assembly and Annual Meeting, November 27 - December 2, 2005 ,Chicago IL. http://archive.rsna.org/2005/4413299.html