Development of transcranial sonothrombolysis as an alternative stroke therapy: incremental scientific advances toward overcoming substantial barriers

Abstract

Transcranial ultrasound and high intensity focused ultrasound technologies have been developed as a method of thrombolysis to be applied to the treatment of acute ischemic stroke. The originating idea to apply ultrasound to treat disease states dates back from the 1930s to 1940s when seminal research findings suggested that ultrasound could have an effect on biological systems and the brain, but the mechanism(s) involved in the effects were unknown. This exciting field of research has flourished since the potential exists to effectively utilize ultrasound to induce thrombolysis noninvasively or perhaps in combination with a thrombolytic agent, such as tissue plasminogen activator or secondary pharmaceutical such as microbubbles to promote cerebral reperfusion and clinical improvement. While there is great enthusiasm in this field of stroke treatment, specific parameters required for optimal sonothrombolysis such as output power, duty cycle, pulse width, and exposure time, as well as the impact of skull bone characteristics and flow mechanics, remain to be defined. This article analyzes relevant ultrasound studies to provide a synthesis of insight in the field of sonothrombolysis to attempt to provide direction for possible future use in stroke patients.

Keywords::

• acute ischemic stroke
• focused ultrasound
• microbubbles
• neuroprotection
• sonothrombolysis
• transcranial

Financial & competing interests disclosure

PA Lapchak is Director of Translational Research and is funded by an NIH NINDS U01 translational research grant NS060685. K Kikuchi is a Visiting Scientist funded by Kurume University School of Medicine. P Butte is Assistant Professor and Director of a Fluorescence Imaging Laboratory. T Hölscher is Director of the Brain Ultrasound Research Laboratory and is funded by an NIH R01 grant R01HL091043. T Hölscher has received funding from InSightec, Inc. (Tirat Carmel, Israel) to develop ultrasound technology, and has ongoing industrial collaborations to develop ultrasound technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was used in the production of this manuscript.