Effects of varying duty cycle and pulse width on high-intensity focused ultrasound (HIFU)-induced transcranial thrombolysis.

Thilo Hölscher,Rema Raman,David J Fisher,Eyal Zadicario,Golnaz Ahadi,Arne Voie

doi:10.1186/2050-5736-1-18

Abstract

The goal was to test the effects of various combinations of pulse widths (PW) and duty cycles (DC) on high-intensity focused ultrasound (HIFU)-induced sonothrombolysis efficacy using an in vitro flow model. An ExAblate™ 4000 HIFU headsystem (InSightec, Inc., Israel) was used. Artificial blood clots were placed into test tubes inside a human calvarium and exposed to pulsatile flow. Four different duty cycles were tested against four different pulse widths. For all study groups, an increase in thrombolysis efficacy could be seen in association with increasing DC and/or PW (p < 0.0001). Using transcranial HIFU, significant thrombolysis can be achieved within seconds and without the use of lytic drugs in vitro. Longer duty cycles in combination with longer pulse widths seem to have the highest potential to optimize clot lysis efficacy.

Highlights

Reversible disaggregation of fibrin fibers, improved distribution of plasminogen, tissue plasminogen activator within a blood clot, and cavitational mechanisms have been described to explain why ultrasound enhances clot lysis [1,2,3,4,5]
The goal of this study was to investigate the impact of varying duty cycles and pulse width on high-intensity focused ultrasound (HIFU)-induced thrombolysis efficacy, in the absence of tissue plasminogen activator (tPA), in a transcranial in vitro flow model
Using transcranial HIFU, significant thrombolysis can be achieved within seconds and without the use of lytic drugs

Summary

Introduction

Reversible disaggregation of fibrin fibers, improved distribution of plasminogen, tissue plasminogen activator (tPA) within a blood clot, and cavitational mechanisms have been described to explain why ultrasound enhances clot lysis [1,2,3,4,5]. Clinical studies on transcranial sonothrombolysis in stroke patients using diagnostic ultrasound devices were promising. Other studies showed comparable results [7,8,9,10,11,12], suggesting that the use of transcranial diagnostic ultrasound in combination with tPA shortens the time to recanalize vessels significantly. The successful use of HIFU for sonothrombolysis outside the cranium and without the additional use of lytic agents, such as tPA, has been described earlier [13]. The goal of this study was to investigate the impact of varying duty cycles and pulse width on HIFU-induced thrombolysis efficacy, in the absence of tPA, in a transcranial in vitro flow model

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Discussion

Conclusion