Sonothrombolysis In Stroke Research Articles

Taboos and opportunities in sonothrombolysis for stroke

Systemic thrombolysis with tissue plasminogen activator (tPA) is the only approved treatment for acute ischaemic stroke that improves functional outcome if given up to 4.5 h from symptom onset. At least half of treated patients have unfavourable outcomes long-term though, emphasising the need to amplify the only approved acute stroke therapy. Ultrasound targeting of an intra-arterial occlusive clot and delivering mechanical pressure to its surrounding fluids (referred to as sonothrombolysis) accelerates the thrombolytic effect of tPA. Higher recanalisation rates produce a trend towards better functional outcomes that could be safely achieved with the combination of 2 MHz frequency ultrasound and systemic tPA. To further accelerate the clot-dissolving effect of ultrasound, a variety of frequencies and intensities as well as other adjuvant treatment elements are being studied. However, literature reports argue efficacy and safety of these novel approaches doubting promptly translation into the clinical practice. This review will summarise our current knowledge about potentially harmful (taboos) directions and what we think are promising avenues for these future stroke therapies. We also give a prospect for novel technologies such as operator-independent devices that aim to further spread the use of sonothrombolysis for stroke.

Noninvasive Transcranial Clot Lysis Using High Intensity Focused Ultrasound

Background: Initial data using transcranial ultrasound in combination with tissue Plasminogen Activator (tPA) for sonothrombolysis in stroke are promising. However, absorption and defocusing of the ultrasound beam occur during transskull insonation, limiting the efficiency of this approach to high extent. The purpose of this in vitro study was to investigate whether transcranial sonothrombolysis can be achieved using High Intensity Focused Ultrasound (HIFU) without the use of tPA. Methods and Results: Transskull clot lysis (N=420) using a novel HIFU head system was performed using an in vitro flow model. Experiments were performed using varying acoustic output powers, changing flow conditions, and different cadaveric skulls. Human whole blood clots (3 hours incubation) could be lysed within less than 30 seconds and in absence of further lytic agents. Thrombolysis efficacy was dependent on transskull signal absorption, acoustic output power and flow conditions and differed widely between a minimum of 6.21% and a maximum of 77.26%. Transskull insonation with HIFU did not lead to significant focus beam distortion. Conclusions: The use of transskull HIFU for immediate clot lysis without the need of further drugs and disregarding individual skull bone characteristics is feasible in vitro.

Transcranial Sound Field Characterization

In the scope of therapeutic ultrasound applications in the adult brain, such as sonothrombolysis in stroke, a better understanding of the intracranial acoustic properties during insonation through the temporal bone is warranted. Innovative ultrasound imaging techniques, like transcranial duplex sonography, may open new avenues to apply ultrasound for therapeutic purposes and to visually monitor the effect using the same device. The aim was to study the transcranial sound field aberrations and the changes of acoustic parameters, using a high-end duplex machine. Six cadaver skulls were insonated through the temporal bone window, using a diagnostic duplex ultrasound device. The measurements were done in a water tank, using a needle hydrophone to assess and compute acoustic parameters, such as peak intensity, peak-to-peak, peak-positive, peak-negative acoustic pressure, beam area etc. in a 2-D plane. It could be shown that the absorption and wavefront distortion effects of the temporal bone are variable among different skulls. Because of signal absorption of the bone, the mechanical index of the incident ultrasound wave drops by a factor ≥10 in most cases. However, the beam area might be increased by a factor of almost 4, because of phase aberration ( i.e., defocusing). (E-mail: thoelscher@ucsd.edu)