Blood-Brain Barrier Disruption by Low-Frequency Ultrasound

Abstract

HomeStrokeVol. 38, No. 2Blood-Brain Barrier Disruption by Low-Frequency Ultrasound Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBBlood-Brain Barrier Disruption by Low-Frequency Ultrasound Tibo Gerriets, MD and Maureen Walberer, DVM Max Nedelmann, MD Georg Bachmann, MD Manfred Kaps, MD Tibo GerrietsTibo Gerriets Department of Neurology, Justus Liebig University Giessen, Giessen, Germany, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author and Maureen WalbererMaureen Walberer Department of Neurology, Justus Liebig University Giessen, Giessen, Germany, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author Max NedelmannMax Nedelmann Department of Neurology, Johannes Gutenberg-University Mainz, Mainz, Germany Search for more papers by this author Georg BachmannGeorg Bachmann Department of Radiology, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author Manfred KapsManfred Kaps Department of Neurology, Justus Liebig University Giessen, Giessen, Germany Search for more papers by this author Originally published14 Dec 2006https://doi.org/10.1161/01.STR.0000254444.19772.33Stroke. 2007;38:251Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 14, 2006: Previous Version 1 To the Editor:Dr Reinhard and coworkers report a case of cerebral gadolinium extravasation after 300 kHz ultrasound “treatment” using the same device that has been applied in the Transcranial Low-Frequency Ultrasound Mediated Thrombolysis in Brain Ischemia Study (TRUMBI) trial.1,2 This interesting observation improves our understanding of the underlying pathophysiology of the hemorrhagic complications that occurred in stroke patients during the TRUMBI study. The assumption that low-frequency ultrasound might cause blood-brain barrier disruptions and thus increase the risk of intracerebral hemorrhage—particularly in the presence of recombinant tissue plasminogen activator—appears convincing and is corroborated by our rat experiments using 20 kHz ultrasound.3 In this MRI study, low-frequency insonation caused a dose-dependant increase in T2-relaxation time which serves as an indicator for vasogenic brain edema and thus indicates blood-brain barrier disruption. Increased ultrasound energy, furthermore, caused circumscript cortical hemorrhagic lesions that appeared like traumatic cerebral contusions histologically. These findings suggest that mechanical ultrasound effects might be responsible for blood-brain barrier disruptions and bleeding complications. Because mechanical effects decrease with higher frequencies, we would recommend the use of ultrasound frequencies in the upper kHz range (ie, >300 kHz) for treatment purposes. Extensive preclinical evaluation of new devices, however, is obligatory.DisclosuresNone.1 Reinhard M, Hetzel A, Kruger S, Kretzer S, Talazko J, Ziyeh S, Weber J, Els T. Blood-brain barrier disruption by low-frequency ultrasound. Stroke. 2006; 37: 1546–1548.LinkGoogle Scholar2 Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, Sedlaczek O, Koroshetz WJ, Hennerici MG. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005; 36: 1441–1446.LinkGoogle Scholar3 Schneider F, Gerriets T, Walberer M, Mueller C, Rolke R, Eicke BM, Bohl J, Kempski O, Kaps M, Bachmann G, Dieterich M, Nedelmann M. Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats. Stroke. 2006; 37: 1301–1306.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Teng Y, Jin H, Nan D, Li M, Fan C, Liu Y, Lv P, Cui W, Sun Y, Hao H, Qu X, Yang Z and Huang Y (2018) In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model, Bioactive Materials, 10.1016/j.bioactmat.2017.08.001, 3:1, (102-109), Online publication date: 1-Mar-2018. Fan L, Liu Y, Ying H, Xue Y, Zhang Z, Wang P, Liu L and Zhang H (2010) Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultrasound Irradiation In Vitro, Journal of Molecular Neuroscience, 10.1007/s12031-010-9479-x, 43:3, (541-548), Online publication date: 1-Mar-2011. Kyle A (2010) Correlation of acoustic pressure with BBB disruption 2010 39th Annual Ultrasonic Industry Association Symposium (UIA), 10.1109/UIA.2010.5506063, 978-1-4244-7947-4, (1-3) Nedelmann M, Gerriets T and Kaps M (2008) Therapeutische Ultraschallbehandlung des akuten HirnarterienverschlussesTherapeutic ultrasound of acute cerebral artery occlusion, Der Nervenarzt, 10.1007/s00115-008-2550-y, 79:12, (1399-1406), Online publication date: 1-Dec-2008. Nedelmann M, Reuter P, Walberer M, Sommer C, Alessandri B, Schiel D, Ritschel N, Kempski O, Kaps M, Mueller C, Bachmann G and Gerriets T (2008) Detrimental Effects of 60 kHz Sonothrombolysis in Rats with Middle Cerebral Artery Occlusion, Ultrasound in Medicine & Biology, 10.1016/j.ultrasmedbio.2008.06.003, 34:12, (2019-2027), Online publication date: 1-Dec-2008. February 2007Vol 38, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000254444.19772.33PMID: 17170362 Originally publishedDecember 14, 2006 PDF download Advertisement