Investigating Sonothrombolysis With High Frequency Ultrasound

Despite a significant body of work establishing the feasibility of ultrasound mediated thrombolysis in vitro, in vivo, and in clinical settings, there remains considerable uncertainty about the specific mechanisms involved in this process. This motivates further work to elucidate these mechanisms, which will be central to optimizing safe and effective operating conditions, and to guide the development of novel approaches and instrumentation. In this study, we investigate the use of high frequency ultrasound as a means of gaining mechanistic insight into sonothrombolysis. A high frequency ultrasound (20-50 MHz) instrument is employed which provides the ability to conduct volumetric clot imaging as well as pulsed-wave Doppler to monitor hemodynamics within vessels and clots. With modifications, it is enabled to perform the acquisition of RF data to assess the displacement of clots and vessel walls subjected to therapeutic pulses. Additional modifications were made to perform nonlinear imaging of micron to submicron sized bubbles, which are of interest in enhancing clot lysis. Experiments were performed on in vitro clots, and in vivo using a rabbit femoral artery clot model initiated by the injection of thrombin. Therapeutic pulses are provided by a single element spherically focused air backed transducer with transmit frequencies of 1.68 MHz. Clear visualization of the clots, displacements, and presence or absence of flow within these vessels is shown to be feasible, indicating the potential of this approach as a tool for providing insight into sonothrombolysis.