Translational Stroke Research

, Volume 2, Issue 2, pp 159–170

Sonothrombolysis: An Emerging Modality for the Treatment of Acute Ischemic and Hemorrhagic Stroke

  • Azita Soltani
  • Wayne M. Clark
  • Douglas R. Hansmann


To date, it is believed that rapid removal of impedances hindering normal blood circulation in the brain would salvage ischemic tissue. Hence, most treatment modalities undergoing clinical evaluation for treatment of stroke are focused on faster recanalization in acute ischemic stroke or faster hematoma mass reduction in hemorrhagic stroke. Therapeutic ultrasound is among the promising emerging modalities being clinically evaluated to meet this purpose. This review provides an overview of existing clinical data in evaluating sonothrombolysis applications in treatment of acute ischemic and hemorrhagic stroke. Furthermore, the present status of clinical evaluation of microbubbles as a potential adjuvant to this modality is reviewed.


Transcranial sonothrombolysis Endovascular sonothrombolysis Acute ischemic stroke Hemorrhagic stroke 



Acute Ischemic Stroke

Barthel Index



Evaluating accelerated resolution of intraventricular hemorrhage, rt-PA (Cathflo®) treatment of brain hemorrhage


Combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA


X-ray computed tomography


External ventricular drain


Food and Drug Administration


Glascow Coma Scale


Hemorrhagic infarction




Intracerebral hemorrhage


Interventional Management of Stroke




Intraventricular hemorrhage


Mechanical Embolus Removal in Cerebral Embolism


Minimally Invasive Surgery Plus t-PA for Intracerebral Hemorrhage Evacuation


Magnetic resonance imaging


Modified Rankin Scale


National Institutes of Health Stroke Scale


National Institute of Neurological Disorders and Stroke


Recombinant tissue plasminogen activator


Standard error of mean


Symptomatic intracerebral hemorrhage


Safety of Lysis with EKOS Ultrasound in the Treatment of ICH and ICH


Transcranial color-coded Doppler


Transcranial color-coded sonography


Transcranial Doppler


Transcranial Low-Frequency Ultrasound-Mediated Thrombolysis in Brain Ischemia


Transcranial Ultrasound in Clinical Sonothrombolysis


Ultrasound contrast agent


  1. 1.
    Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, Bushnell CD, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Stroke. 2006;37:1583–633.PubMedGoogle Scholar
  2. 2.
    MacKay J, Mensah G. Atlas of heart disease and stroke. Geneva: World Health Organization; 2004.Google Scholar
  3. 3.
    del Zoppo G, Poeck K, Pessin M, Wolpert SM, Furlan AJ, Ferbert A, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann of Neurol. 1992;32:78–85.CrossRefGoogle Scholar
  4. 4.
    Fieschi C, Argentino C, Lenzi G, Sacchetti M, Toni D, Bozzao L. Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. J Neurol Sci. 1989;91:311–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Watenberg KE, Mayer SA. Reducing the risk of ICH enlargement. J Neurol Sci. 2007;261:99–107.CrossRefGoogle Scholar
  6. 6.
    Hallevi H, Albright KC, Aronowski J, Barreto AD, Martin-Schild S, Khaja AM, et al. Intraventricular hemorrhage: anatomic relationships and clinical implications. Neurology. 2008;70:848–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Young W, Lee KP, Pessin MS, Kwan ES, Rand WM, Caplan LR. Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study. Neurology. 1990;40:616–9.PubMedGoogle Scholar
  8. 8.
    Report of the Stroke Progress Review Group: National Institute of Health/National Institute of Neurological Disorders and Stroke. (2002). Accessed 7 Dec 2010.
  9. 9.
    Adams Jr HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38:1655–711.PubMedCrossRefGoogle Scholar
  10. 10.
    Del Zoppo GJ, Saver JL, Jauch EC, Adams HP. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40:2945–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Ringleb PA, Bousser MG, Ford G, Bath P, Brainin M, Caso V, et al. Guidelines for management of ischemic stroke and transient ischemic attack 2008. Cerebrovasc Dis. 2008;25:457–507.CrossRefGoogle Scholar
  12. 12.
    European Stroke Organization guideline update, January 2009. (2009). Accessed 1 Dec 2010.
  13. 13.
    Anonymous. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke, rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581–7.CrossRefGoogle Scholar
  14. 14.
    Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359:1317–29.PubMedCrossRefGoogle Scholar
  15. 15.
    Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36:1432–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Anonymous. CAST randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349:1641–9.CrossRefGoogle Scholar
  17. 17.
    International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke. Lancet. 1997;349:1569–81.CrossRefGoogle Scholar
  18. 18.
    Rordorf G, Koroshetz WJ, Ezzeddine MA, Segal AZ, Buonanno FS. A pilot study of drug-induced hypertension for treatment of acute stroke. Neurology. 2001;56:1210–3.PubMedGoogle Scholar
  19. 19.
    Hacke W, Albers G, Al-Rawi Y. The Desmoteplase in acute ischemic stroke trial (DIAS). A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005;36:66–73.PubMedCrossRefGoogle Scholar
  20. 20.
    Parsons MW, Miteff F, Bateman GA, Spratt N, Loiselle A, Attia J, et al. Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window. Neurology. 2009;72:915–21.PubMedCrossRefGoogle Scholar
  21. 21.
    Pancioli AM, Broderick J, Brott T, Tomsick T, Khoury J, Bean J, et al. The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial. Stroke. 2008;39:3268–76.PubMedCrossRefGoogle Scholar
  22. 22.
    Ginsberg MD, Hill MD, Palesch YY, Ryckborst KJ, Tamariz D. The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke—I: physiological responses and safety results. Stroke. 2006;37:2100–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Palesch YY, Hill MD, Ryckborst KJ, Tamariz D, Ginsberg MD. The ALIAS pilot trial: a dose-esclation and safety study of albumin therapy for acute ischemic stroke—II: neurologic outcome and efficacy analysis. Stroke. 2006;37:2107–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose finding study. Stroke. 2010;41:2283–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Saver JL, Kidwell C, Eckstein M, Starkman S, FAST-MAG Pilot Trial Investigators. Prehospital neuroprotective therapy for acute stroke: results of the Field Administration of Stroke-Therapy Magnesium (FAST-MAG) pilot trial. Stroke. 2004;35:e106–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Otomo E et al. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 2003;15:222–9.CrossRefGoogle Scholar
  27. 27.
    Kulcsar Z, Bonvin C, Pereira VM, Altrichter S, Yilmaz H, Loevblad KO, et al. Penumbra system: a novel mechanical thrombectomy device for large-vessel occlusions in acute stroke. Am J Neuroradiol. 2010;31:628–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Castano C, Dorado L, Guerrero C, Millan M, Gomis M, Perez de la Ossa N, et al. Mechanical thrombectomy with the solitaire AB device in large artery occlusions of the anterior circulation. Stroke. 2010;41:1836–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Shuaib A, Sentis Steering Committee. SENTIS: a randomized trial evaluating vertebral perfusion augmentation via partial aortic occlusion in acute ischemic stroke. 7th World Stroke Congress; 2010 16 Oct 2010; Abstract 1154Google Scholar
  30. 30.
    Gonzalez A, Mayol A, Martinez E, Gonzalez-Marcos JR, Gil-Peralta A. Mechanical thrombectomy with snare in patients with acute ischemic stroke. Neuroradiology. 2007;49:365–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Mayer TE, Hamann GF, Brueckmann HJ. Treatment of basilar artery embolism with a mechanical extraction device. Stroke. 2002;33:2232–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L). Final results. Stroke. 2010;41:2265–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B, Devlin T, et al. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009;40:1359–64.PubMedCrossRefGoogle Scholar
  34. 34.
    Morgenstern LB, Hemphill JC, Anderson C, Becker K, Broderick JP, Es Jr Connolly, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41:2108–29.PubMedCrossRefGoogle Scholar
  35. 35.
    Steiner T, Katse M, Forsting M, Mendelow D, Kwiecinski H, Szikora I, et al. Recommendations for the management of intracranial haemorrhage-part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis. 2006;22:294–316.PubMedCrossRefGoogle Scholar
  36. 36.
    Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.PubMedCrossRefGoogle Scholar
  37. 37.
    Morgan T, Awad I, Keyl P, Lane K, Hanley DF. Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl. 2008;105:217–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Alexandrov AV, Burgin WS, Demchuk AM, El-mitwalli A, Grotta JC. Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement. Circulation. 2001;103:2897–902.PubMedGoogle Scholar
  39. 39.
    Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;38:967–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Kornowski R, Meltzer RS, Chernine A, Vered Z, Battler A. Does external ultrasound accelerate thrombolysis? Results from a rabbit model. Circulation. 1994;89:339–44.PubMedGoogle Scholar
  41. 41.
    Tachibana K, Tachibana S. Prototype therapeutic ultrasound emitting catheter for accelerating thromblolysis. J Ultrasound Med. 1997;16:529–35.PubMedGoogle Scholar
  42. 42.
    Olsson SB, Johansson B, Nilsson AM, Olsson Ch, Roijer A. Enhancement of thrombolysis by ultrasound. Ultrasound Med Biol. 1994;20:375–82.PubMedCrossRefGoogle Scholar
  43. 43.
    Cintas P, Le Traon AP, Larrue V. High rate of recanalization of middle cerebral artery occlusion during 2-MHz transcranial color-coded Doppler continuous monitoring without thrombolytic drug. Stroke. 2002;33:626–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Francis CW, Oenunderson PT, Carstensen EL, Blinc A, Meltzer RS. Enhancement of fibrinolysis in vitro by ultrasound. J Clin Invest. 1992;90:2063–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Luo H, Nishioka T, Fishbein MC, Cercek B, Forrester JS, Kim CJ, et al. Transcutaneous ultrasound augments lysis of arterial thrombi in vivo. Circulation. 1996;94:775–8.PubMedGoogle Scholar
  46. 46.
    Anonymous. Assessment: transcranial Doppler. Report of the American Academy of Neurology, Therapeutics and Technology Assessment Subcommittee. Neurology. 1990;40:680–1.Google Scholar
  47. 47.
    Postert T, Federlein J, Przuntek H, Buettner T. Insufficient and absent acoustic temporal bone window: potential and limitations of transcranial contrast-enhanced color-coded sonography and contrast-enhanced power-based sonography. Ultrasound Med Biol. 1997;23:857–62.PubMedCrossRefGoogle Scholar
  48. 48.
    Alexandrov AV, Demchuk AM, Felberg RA, Christou I, Barber PA, Burgin WS, et al. High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial Doppler monitoring. Stroke. 2000;31:610–4.PubMedGoogle Scholar
  49. 49.
    Aexandrov AV, Demchuk AM, Burgin S, Robinson DJ, Grotta JC, et al. Ultrasound-enhanced thrombolysis for acute ischemic stroke: phase I. Finding of the CLOTBUST trial. J Neuroimaging. 2004;14:113–7.Google Scholar
  50. 50.
    Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004;351:2170–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Pfaffenberger S, Devcic-Kuhar B, Kollmann C, Kastl SP, Kaum C, Speidl WS, et al. Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model. Stroke. 2005;36:124–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Swiercz M, Swiat M, Pawlak M, Weigele J, Tarasewicz R, Sobolewski A, et al. Narrowing of the middle cerebral artery: artificial intelligence methods and comparison of transcranial color coded duplex sonography with conventional TCD. Ultrasound Med Biol. 2010;36:17–28.PubMedCrossRefGoogle Scholar
  53. 53.
    Eggers J, Koch B, Meyer K, König I, Seidel G. Effect of ultrasound on thromobolysis of middle cerebral artery occlusion. Ann Neurol. 2003;53:797–800.PubMedCrossRefGoogle Scholar
  54. 54.
    Eggers J, Koenig IR, Koch B, Händler G, Seidel G. Sonothrombolysis with transcranial color-coded sonography and recombinant tissue-type plasminogen activator in acute middle cerebral artery main stem occlusion: results from a randomized study. Stroke. 2008;39:1470–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Eggers J, Sedel G, Koch B, König IR. Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA. Neurology. 2005;64:1052–4.PubMedGoogle Scholar
  56. 56.
    Siddiqi F, Odrljin TM, Fay PJ, Cox C, Francis CW. Binding of tissue-plasminogen activator to fibrin: effect of ultrasound. Blood. 1998;91:2019–25.PubMedGoogle Scholar
  57. 57.
    Braaten JV, Goss RA, Francis CW. Ultrasound reversibly disaggregates fibrin fibers. Thromb Haemost. 1997;78:1063–8.PubMedGoogle Scholar
  58. 58.
    Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, et al. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemic: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005;36:1441–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Hölscher T, Wilkening WG, Molkenstruck S, Voit H, Koch C. Transcranial sound field characterization. Ultrasound Med Biol. 2008;34:973–80.PubMedCrossRefGoogle Scholar
  60. 60.
    Apfel RE, Holland CK. Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound. Ultrasound Med Biol. 1991;17:179–85.PubMedCrossRefGoogle Scholar
  61. 61.
    Datta S, Coussios CC, McAdory LE, Porter T, De Courten-Myers G, et al. Correlation of cavitation with ultrasound enhancement of thrombolysis. Ultrasound Med Biol. 2006;32:1257–67.PubMedCrossRefGoogle Scholar
  62. 62.
    Deng CX, Xu Q, Apfel Re, Holland CK. In vitro measurement of inertial cavitation thresholds in human blood. Ultrasound Med Biol. 1996;22:939–48.PubMedCrossRefGoogle Scholar
  63. 63.
    Mahon BR, Nesbit GM, Barnwell SL, Clark W, Marotta TR, Weill A, et al. North American clinical experience with the EKOS MicroLysUS infusion catheter for the treatment of embolic stroke. Am J Neuroradiol. 2003;24:534–8.PubMedGoogle Scholar
  64. 64.
    Furlan AJ. Acute stroke therapy: beyond IV tPA. Cleve Clin J Med. 2002;69:730–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Jones MM, Nogajski JH, Faulder K, Harrington T, Ng P, Storey CE. Intra-arterial thrombolysis in acute ischemic stroke. Intern Med J. 2005;35:300–2.PubMedCrossRefGoogle Scholar
  66. 66.
    IMS II trial investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007;38:2127–35.CrossRefGoogle Scholar
  67. 67.
    Khatri P, Hill MD, Palesch YY, Spilker J, Jauch EC, Carrozzella JA, et al. Methodology of the interventional management of stroke III trial. Int J Stroke. 2008;3:130–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Newell DW, Shah M, Wilcox R, Hansmann D, Hanley DF. Sonothrombolysis is effective for minimally invasive evacuation of spontaneous Intracerebral hemorrhage. International Stroke Conference (ISC); 2010 25 Feb 2010; Abstract 192.Google Scholar
  69. 69.
    Tachibana K, Tachibana S. Albumin microbubble echo-contrast material as an enhancer or ultrasound accelerated thrombolysis. Circulation. 1995;92:1148–50.PubMedGoogle Scholar
  70. 70.
    Porter TR, Xie F, Kricsfeld A, Kilzer K. Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropropane-exposed sonicated dextrose albumin. J Am Coll Cardiol. 1995;26:33–40.PubMedCrossRefGoogle Scholar
  71. 71.
    Lou H, Nishioka T, Bar-Cohen Y, Berglund H, Kim CJ, Fishbein MC, et al. Transcutaneous ultrasound, low dose streptokinase and echogen are synergistic for the lysis of in vivo thrombotic occlusion. J Am Coll Cardiol. 1997;29(Supplement 1):478A–9A.Google Scholar
  72. 72.
    Wu Y, Unger EC, McCreery TP, Sweitzer RH, Shen D, Wu G, et al. Binding and lysing of blood clots using MRX-408. Invest Radiol. 1998;33:880–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Kondo I, Mizushige K, Ueda T, Masugata H, Ohmori K, Matsuo H. Histological observations and the process of ultrasound contrast agent enhancement of tissue plasminogen activator thrombolysis with ultrasound exposure. Jpn Circ J. 1999;63:478–84.PubMedCrossRefGoogle Scholar
  74. 74.
    Mizushige K, Kondo I, Ohmori K, Hirao K, Matsuo H. Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure. Ultrasound Med Biol. 1999;25:1431–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Cintas P, Nguyen F, Boneu B, Larrue V. Enhancement of enzymatic fibrinolysis with 2-MHz ultrasound and microbubbles. J Thromb Haemost. 2004;2:1163–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Nishioka T, Luo H, Fishbein MC, Cercek B, Forrester JS, Kim CJ, et al. Dissolution of thrombotic arterial occlusion by high intensity, low frequency ultrasound and dodecafluoropentane emulsion: an in vitro and in vivo study. J Am Coll Cardiol. 1997;30:561–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Birnbaum Y, Luo H, Nagai T, Fishbein MC, Peterson TM, Li S, et al. Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles. Circulation. 1998;97:130–4.PubMedGoogle Scholar
  78. 78.
    Culp WC, Porter TR, Lowery J, Xie F, Roberson PK, Marky L. Intracranial clot lysis with intravenous microbubbles and transcranial ultrasound in swine. Stroke. 2004;35:2407–11.PubMedCrossRefGoogle Scholar
  79. 79.
    Dalecki D, Raeman CH, Child SZ, Cox C, Francis CW, Meltzer RS, et al. Hemolysis in vivo from exposure to pulsed ultrasound. Ultrasound Med Biol. 1997;23:307–13.PubMedCrossRefGoogle Scholar
  80. 80.
    Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K. Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol. 2004;30:979–89.PubMedCrossRefGoogle Scholar
  81. 81.
    Meairs S, Alonso A. Ultrasound, microbubbles and the blood brain barrier. Prog Biophys Mol Biol. 2007;93:354–62.PubMedCrossRefGoogle Scholar
  82. 82.
    Molina CA, Ribo M, Rubiera M, Montaner J, Santamarina E, Delgado-Mederos R, et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke. 2006;37:425–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Rubiera M, Ribo M, Delgado-Mederos R, Santamarina E, Maisterra O, Delgado P, et al. Do bubble characteristics affect recanalization in stroke patients treated with microbubble-enhanced sonothrombolysis? Ultrasound Med Biol. 2008;34:1573–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Dinia L, Rubiera M, Ribo M, Maisterra O, Ortega G, del Sette M, et al. Reperfusion after stroke sonothrombolysis with microbubbles may predict intracranial bleeding. Neurology. 2009;73:775–80.PubMedCrossRefGoogle Scholar
  85. 85.
    Alexandrov AV, Mikulik R, Ribo M, Sharma VK, Lao AY, Tsivgoulis G, et al. A pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perflutren-lipid microspheres for acute ischemic stroke. Stroke. 2008;39:1464–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Perren F, Loulidi J, Poglia D, Landis T, Sztajzel R. Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis in acute stroke. J Thromb Thrombolysis. 2008;25:219–23.PubMedCrossRefGoogle Scholar
  87. 87.
    Molina Ca, Barreto AD, Tsivgoulis G, Sierzenski P, Malkoff MD, Rubiera M, et al. Transcranial ultrasound in clinical sonothrombolysis (TUCSON) trial. Ann Neurol. 2009;66:28–38.PubMedCrossRefGoogle Scholar
  88. 88.
    Prokop AF, Soltani A, Roy RA. Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol. 2007;33:942–33.CrossRefGoogle Scholar
  89. 89.
    Hajri Z, Boukadoum M, Hamam H, Fontaine R. An investigation of the physical forces leading to thrombosis disruption by cavitation. J Thromb Thrombolysis. 2005;20:27–32.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Azita Soltani
    • 1
  • Wayne M. Clark
    • 2
  • Douglas R. Hansmann
    • 1
  1. 1.Research and Development DepartmentEKOS CorporationBothellUSA
  2. 2.Oregon Stroke Center, Oregon Health Sciences UniversityPortlandUSA

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