MR-guided focused ultrasound for acute stroke: a rabbit model.

R ecent developments in thrombolysis therapy using tissue Plasminogen Activator (tPA) in combination with ultrasound for noninvasive stroke treatment are of great excitement. The first clinical trials have been successfully initiated, demonstrating the potential benefit of transcranial ultrasound in combination with tPA as an effective vessel recanalizing treatment strategy. 6–10 The use of tPA, however, is limited because of its various exclusion criteria, its availability , and its costs. Depending on the literature, the number of patients with stroke receiving tPA treatment ranges between 1.6% 11 and 9%, 12 averaging 3% to 4% worldwide. Hence, novel treatment options in stroke are in high demand. Neurointerventional methods for mechanical clot retrieval in acute stroke show great potential 13–16 but are currently limited to highly specialized centers. Alternative strategies to treat stroke noninvasively and in the absence of tPA might be provided by innovative ultrasound technologies, such as tran-scranial focused ultrasound (FUS). First investigations in this regard have emphasized the high potential of successful clot lysis in combination with 17,18 but, more so, in the absence of tPA. Very recently, successful transcranial clot lysis within seconds and without the use of tPA has been demonstrated using one of the first transcranial FUS head systems worldwide , designed for therapeutic FUS applications in humans. 21 In the following report, the results of recent in vitro studies, first in vivo data using a novel sonothrombolysis model, and a future concept for potential transcranial FUS therapy in stroke will be presented. equipped with a transcranial hemispheric transducer, has been used for all studies. In the clinical setup, the FUS system is integrated into an MRI scanner (Figure 1). Because the ExAblate 4000 is a purely therapeutic device without imaging capability, MRI is used for focus beam visualization using MR thermometry and neuronavigation in the 3-dimensional space. The system has been developed for brain applications in humans. The key component of this system is a hemispheric phased array transducer with 1000 single piezo elements, which can be operated independently. The transmit frequency of the ExAblate 4000 is 220 kiloHertz. The hemispheric geometry of the FUS transducer allows ultrasound transmission across the entire skull. All 1000 beams are focused at the geometric center of the transducer, producing a sharp focus (radius, 2.0 mm in X/Y-and 3.0 mm in Z-orientation). The focus can be steered electronically in a radius of 3.0 cm in any direction without considerable phase …