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The Role of Cavitation in Enhancement of rt-PA Thrombolysis

DATTA, SAURABH
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1196034787

Abstract Details

2007, PhD, University of Cincinnati, Engineering : Biomedical Engineering.
Pulsed ultrasound, when used as an adjuvant to a thrombolytic, such as recombinant tissue plasminogen activator (rt-PA), could enhance therapeutic efficacy. Such enhancement would represent a significant breakthrough in the treatment of diseases like ischemic stroke, myocardial infarction, pulmonary embolism and deep vein thrombosis. Acoustic cavitation was hypothesized in this work to be the underlying mechanism responsible for thrombolytic enhancement. Existing theoretical models were employed to predict rectified diffusion and cavitation thresholds at 120 kHz. Stable and inertial cavitation thresholds were measured experimentally and clots were exposed to cavitational activity in the presence of rt-PA. Subsequently, an approach for cavitation nucleation using infusion of a contrast agent was tested experimentally in vitro. Finally, a technique for stable cavitation monitoring was developed which tracks the ultraharmonic emissions during the combined ultrasound and thrombolytic exposures in a human blood clot model. The stable cavitation activity was measured during clot mass loss experiments. A dual antibody immunofluorescence technique was employed to measure penetration depths of rt-PA and plasminogen into the clots. Porcine whole blood clots, when exposed to stable cavitation activity in the presence of rt-PA, resulted in the highest mass loss of 26.0 ± 4 %. The presence of inertial cavitation lowered the mass loss to 20.7 ± 1.6 %. A commercial contrast agent, Definity®, was successfully used to promote and sustain the nucleation of stable cavitation during pulsed ultrasound exposure at 120 kHz for 30 min. The largest clot mass loss of 26.2 ± 2.6 % was observed in human whole blood clots in the presence of sustained stable cavitation activity. A significant correlation was observed between clot mass loss and ultraharmonic signals (r=0.8549, p<0.0001, n=24). The largest mean penetration depth of rt-PA (222 µm) and plasminogen (241 µm) was observed in the presence of stable cavitation activity. Significant enhancement of thrombolysis correlated with the presence of cavitation activity and stable cavitation plays an important role in this enhancement.
Dr. Christy Holland (Advisor)
145 p.
Thrombolysis; Ultrasound-assisted Thrombolysis; Therapeutic Ultrasound; Stroke; Cavitation; Stable Cavitation; Tissue Plasminogen Activator; Drug Delivery

Recommended Citations

Citations

  • DATTA, S. (2007). The Role of Cavitation in Enhancement of rt-PA Thrombolysis [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1196034787

    APA Style (7th edition)

  • DATTA, SAURABH. The Role of Cavitation in Enhancement of rt-PA Thrombolysis. 2007. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1196034787.

    MLA Style (8th edition)

  • DATTA, SAURABH. "The Role of Cavitation in Enhancement of rt-PA Thrombolysis." Doctoral dissertation, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1196034787

    Chicago Manual of Style (17th edition)

ucin1196034787
876
© 2007, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.