Design of a focused ultrasound transducer for histotripsy-thrombolytic combination therapy

Abstract

Chronic thrombus components are resistant to removal by current interventional techniques and can act as thrombogenic sources. Histotripsy is a focused ultrasound therapy that utilizes the mechanical activity of bubble clouds to liquefy target tissues. In vitro experiments have demonstrated histotripsy provides enhancement of the thrombolytic agent recombinant tissue plasminogen activator in a retracted clot model representative of chronic thrombus. Although these in vitro results are promising, further refinement of the acoustic source is necessary for in vivo studies and clinical translation. To define the source parameters for use in vivo, a design study was conducted with transcutaneous exposure of porcine and human iliofemoral deep venous thrombosis (DVT) as the target. Design parameters were selected to confine the focus, and thus bubble activity, within the femoral vein of DVT patients. Furthermore, the therapy array accommodates the placement of a confocal diagnostic linear array for image guidance. Based on the design criteria, a 1.5-MHz elliptical source with 6-cm focal length and a focal gain of 70 was selected. Details of the design, fabrication, and characterization the source will be presented, as well as the means by which bubble activity is initiated.