Can a Commercial Diagnostic Ultrasound Device Accelerate Thrombolysis?

Pfaffenberger, Stefan; Devcic-Kuhar, Branka; Kollmann, Christian; Kastl, Stefan P.; Kaun, Christoph; Speidl, Walter S.; Weiss, Thomas W.; Demyanets, Svitlana; Ullrich, Robert C.; Sochor, Heinz; Wöber, Christian; Zeitlhofer, J.; Huber, Kurt; Gröschl, Martin; Benes, E.; Maurer, Gerald; Wojta, Johann; Gottsauner‐Wolf, Michael

doi:10.1161/01.str.0000150503.10480.a7

Cited by 81 publications

(38 citation statements)

References 38 publications

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“…Ultrasound power is attenuated through the skull by as much as 99%,13, 14 yet evidence that higher power increases clot lysis15 indicates that power attenuation likely limits the efficacy of intracranial sonothrombolysis. Additionally, there is evidence that low‐frequency ultrasound facilitates clot lysis 15, 16.…”

Section: Discussionmentioning

confidence: 99%

Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis

Tomkins

Hood

Pepperall

et al. 2016

JAHA

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BackgroundStroke associated with acute carotid occlusion is associated with poor effectiveness of tissue plasminogen activator (tPA) thrombolysis and poor prognosis. Rupture of atherosclerotic plaques resulting in vascular occlusions may occur on plaques, causing variable stenosis. We hypothesized that degree of stenosis may affect recanalization rates with tPA. Ultrasound+tPA (sonothrombolysis) has been shown to improve recanalization for intracranial occlusions but has not been tested for carotid occlusion. Our primary aim was to determine thrombolytic recanalization rates in a model of occlusion with variable stenosis, with a secondary aim to investigate sonothrombolysis in this model.Methods and ResultsRat carotid arteries were crushed and focal stenosis created (25% baseline Doppler flow) with a silk‐suture tie invoking thrombosis and occlusion. To model mild or severe stenosis, the tie was released pretreatment or left in place. Animals were treated with tPA (10 mg/kg) or tPA+ultrasound (2‐MHz) in each stenosis model (n=7/group). Recanalization was assessed by Doppler flow. Thrombolytic recanalization rates were significantly higher in mild stenosis groups (71% versus 0% with severe stenosis; P<0.0001). Recanalization rates were not significantly higher with additional ultrasound in either model.ConclusionsIn this model, the degree of carotid stenosis had a large effect on thrombolytic recanalization. Sonothrombolysis using standard parameters for intracranial sonothrombolysis did not increase recanalization. Further testing is warranted. The degree of underlying stenosis may be an important predictor of thrombolytic recanalization, and clinical correlation of these findings may provide new approaches to treatment selection for patients with carotid occlusion.

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Section: Discussionmentioning

confidence: 99%

Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis

Tomkins

Hood

Pepperall

et al. 2016

JAHA

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“…20 However, the effect of transcranially applied US emitted by a 1-MHz commercial probe has been shown in vitro, 3 and several clinical investigators have independently found such an effect as well. 6,12,21,22 The additive effects of US on the endothelium could also contribute to the observed clinical results.…”

Section: Discussionmentioning

confidence: 99%

Sonothrombolysis With Transcranial Color-Coded Sonography and Recombinant Tissue-Type Plasminogen Activator in Acute Middle Cerebral Artery Main Stem Occlusion

Eggers

König

Koch

et al. 2008

Stroke

143

144

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Background and Purpose-Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented. Methods-Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control group. All underwent standard thrombolysis with intravenous recombinant tissue-type plasminogen activator. Results-Thirty-seven subjects were included; 19 subjects were treated in the target (US) group and 18 in the control (no-US) group, all with no residual flow in the middle cerebral artery main stem occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with the no-US group, the US group showed greater improvement in National Institutes of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator initiation. Recanalization (complete or partial) after 1 hour occurred in 57.9% of the US group and 22.2% of the no-US group (Pϭ0.045). After 90 days, 4 subjects from the US group had a modified Rankin Score Յ1 (none from the no-US group) and 8 had a Barthel Index Ն95 (none from the no US group; Pϭ0.106 and Pϭ0.003, respectively). Three subjects from the US group (15.8%) developed a symptomatic intracranial hemorrhage as did one (5.6%) in the no-US group (Pϭ0.60). Conclusions-This small randomized study indicates a beneficial impact of transcranial ultrasound on recanalization and short-term outcome in subjects with middle cerebral artery main stem occlusion and recombinant tissue-type plasminogen activator treatment.

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“…The two skulls exhibiting higher ultrasound absorption had underdeveloped mastoid processes. Other in vitro and clinical studies have investigated some cases where the temporal bones were recalcitrant to the penetration of the ultrasound (Kollár et al 2004;Pfaffenberger et al 2005). This lack of ultrasound penetration is referred to as temporal bone window insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Ultrasound Propagation Through Ex-vivo Human Temporal Bone

Ammi

Mast

Huang

et al. 2008

Ultrasound in Medicine & Biology

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Adjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke (Eggers 2006;Tsivgoulis and Alexandrov 2007). The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.03 and 2.00 MHz ultrasound transducers to identify optimal ultrasound parameters that would maximize penetration and minimize aberration of the beam. To achieve this goal, in vitro experiments were conducted on five human skull specimens. In a water-filled tank, two unfocused transducers (0.12 and 1.03 MHz) and one focused transducer (2.00 MHz) were consecutively placed near the right temporal bone of each skull. A hydrophone, mounted on a micropositioning system, was moved to an estimated location of the middle cerebral artery (MCA) origin and measurements of the surrounding acoustic pressure field were performed. For each measurement, the distance from the position of maximum acoustic pressure to the estimated origin of the MCA inside the skulls was quantified. The -3 dB depth of field and beam width in the skull were also investigated as a function of the three frequencies. Results show that the transducer alignment relative to the skull is a significant determinant of the detailed behavior of the acoustic field inside the skull. For optimal penetration, insonation normal to the temporal bone was needed. The shape of the 0.12-MHz intracranial beam was more distorted than those at 1.03 and 2.00 MHz due to the large aperture and beam width. However, lower ultrasound pressure reduction was observed at 0.12 MHz (22.5%). At 1.03 and 2.00 MHz two skulls had an insufficient temporal bone window and attenuated the beam severely (up to 96.6% pressure reduction). For all frequencies, constructive and destructive interference patterns were seen near the contralateral skull wall at various elevations. The 0.12-MHz ultrasound beam depth of field was affected the most when passing Corresponding Address: Christy K. Holland, Ph.D., Department of Biomedical Engineering, Colleges of Medicine and Engineering, University of Cincinnati, Medical Science Building, Rm. 6167, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0586, USA, Phone: +1 (513) 558-5675, Fax: +1 (513) 558-5958, Christy.Holland@uc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript through the temporal bone and showed a decrease in size of more than 55% on average. The speed of sound in the temporal...

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Can a Commercial Diagnostic Ultrasound Device Accelerate Thrombolysis?

Cited by 81 publications

References 38 publications

Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis

Thrombolytic Recanalization of Carotid Arteries Is Highly Dependent on Degree of Stenosis, Despite Sonothrombolysis

Sonothrombolysis With Transcranial Color-Coded Sonography and Recombinant Tissue-Type Plasminogen Activator in Acute Middle Cerebral Artery Main Stem Occlusion

Characterization of Ultrasound Propagation Through Ex-vivo Human Temporal Bone

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