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

Expert Review of Medical Devices

Volumn 10, Issue 2, 2013, Pages 201-213

  Lapchak, Paul A ^a   Kikuchi, Kiyoshi ^a,b   Butte, Pramod ^a   Hölscher, Thilo ^c  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b KURUME UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

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

Indexed keywords

ACUTE ISCHEMIC STROKE; FOCUSED ULTRASOUND; MICROBUBBLES; NEUROPROTECTION; SONOTHROMBOLYSIS; TRANSCRANIAL;

TISSUE; ULTRASONIC TESTING;

ULTRASONICS;

TISSUE PLASMINOGEN ACTIVATOR;

BLOOD CLOT; BLOOD CLOT LYSIS; CEREBROVASCULAR ACCIDENT; DOPPLER ECHOGRAPHY; ELASTICITY; HIGH INTENSITY FOCUSED ULTRASOUND; HUMAN; MICROBUBBLE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; REPERFUSION; REVIEW; SONOTHROMBOLYSIS; STANDARDIZATION; THROMBOCYTE AGGREGATION; THROMBUS;

ANIMALS; CEREBROVASCULAR CIRCULATION; EQUIPMENT DESIGN; FIBRINOLYTIC AGENTS; HIGH-INTENSITY FOCUSED ULTRASOUND ABLATION; HUMANS; MECHANICAL THROMBOLYSIS; MICROBUBBLES; STROKE; THROMBOLYTIC THERAPY; TREATMENT OUTCOME; ULTRASONIC THERAPY;

EID: 84874823119     PISSN: 17434440     EISSN: 17452422     Source Type: Journal    
DOI: 10.1586/erd.12.88     Document Type: Review

References (96)

1. Lloyd-Jones D, Adams RJ, Brown TM et al . Heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation 121 (7), e46 - e215 (2010) .
2. Lloyd-Jones D, Adams RJ, Brown TM et al .; American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Executive summary: heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation 121 (7), 948 - 954 (2010) .
3. Boudreau DM, Guzauskas G, Villa KF, Fagan SC, Veenstra DL. A model of cost- effectiveness of tissue plasminogen activator in patient subgroups 3 to 4.5 hours after onset of acute ischemic stroke. Ann. Emerg. Med. 61 (1), 46 - 55 (2013) .
4. Roger VL, Go AS, Lloyd-Jones DM et al .; American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Heart disease and stroke statistics - 2011 update: a report from the American Heart Association. Circulation 123 (4), e18 - e209 (2011) .
5. Roger VL, Go AS, Lloyd-Jones DM et al .; American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Heart disease and stroke statistics - 2012 update: a report from the American Heart Association. Circulation 125 (1), e2 - e220 (2012) .
6. Hacke W, Kaste M, Bluhmki E et al .; ECASS Investigators . Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N. Engl. J. Med. 359 (13), 1317 - 1329 (2008) .
7. Lansberg MG, Bluhmki E, Thijs VN . Effi cacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis. Stroke 40 (7), 2438 - 2441 (2009) .
8. Sandercock P, Wardlaw JM, Lindley RI et al; IST-3 collaborative group . The benefi ts and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 379 (9834), 2352 - 2363 (2012) .
9. Fang MC, Cutler DM, Rosen AB . Trends in thrombolytic use for ischemic stroke in the United States. J. Hosp. Med. 5 (7), 409 (2010)
10. Francis CW, Onundarson PT, Carstensen EL et al . Enhancement of fi brinolysis in vitro by ultrasound. J. Clin. Invest. 2063 - 2068 (1992) .
11. Braaten JV, Goss RA, Francis CW . Ultrasound reversibly disaggregates fi brin fi bers. Thromb. Haemost. 78 (3), 1063 - 1068 (1997) .
12. Siddiqi F, Odrljin TM, Fay PJ, Cox C, Francis CW . Binding of tissue-plasminogen activator to fi brin: effect of ultrasound. Blood 91 (6), 2019 - 2025 (1998) .
13. Sakharov DV, Rijken DC . The effect of fl ow on lysis of plasma clots in a plasma environment. Thromb. Haemost. 83 (3), 474 (2000) .
14. Datta S, Coussios CC, McAdory LE et al . Correlation of cavitation with ultrasound enhancement of thrombolysis. Ultrasound Med. Biol. 32 (8), 1257 - 1267 (2006) .
15. Prokop AF, Soltani A, Roy RA . Cavitational mechanisms in ultrasound-accelerated fi brinolysis. Ultrasound Med. Biol. 924-933 (2007) .
16. Everbach EC, Francis CW . Cavitational mechanisms in ultrasound- accelerated thrombolysis at 1 MHz. Ultrasound Med. Biol. 26 (7), 1153 - 1160 (2000) .
17. Harvey EN . Biological aspects of ultrasonic waves, a general survey. Biol. Bull. 59, 325 (1930) .
18. Lynn JG, Zwemer RL, Chick AJ, Miller AE. A new method for the generation and use of focused ultrasound in experimental biology. J. Gen. Physiol. 26 (2), 179 - 193 (1942) .
19. Fry WJ, Barnard JW, Fry EJ, Krumins RF, Brennan JF . Ultrasonic lesions in the mammalian central nervous system. Science, 517-518 (1955) .
20. Fry WJ, Barnard JW, Fry FJ, Brennan JF . Ultrasonically produced localized selective lesions in the central nervous system. Am. J. Phys. Med. 34 (3), 413 - 423 (1955) .
21. Bakay L, Ballantine HT Jr, Hueter TF, Sosa D . Ultrasonically produced changes in the blood-brain barrier. AMA Arch. Neurol. Psychiatry 76 (5), 457 - 467 (1956) .
22. Fry WJ, Fry FJ . Fundamental neurological research and human neurosurgery using intense ultrasound. IRE Trans. Med. Electron. ME-7, 166 - 181 (1960) .
23. Fry FJ, Kossoff G, Eggleton RC, Dunn F . Threshold ultrasonic dosages for structural changes in the mammalian brain. J. Acoust. Soc. Am. 48 (6) , Suppl. 2, 1413+ (1970) .
24. Fry FJ, Goss SA . Further studies of the transkull transmission of an intense focused ultrasonic beam: lesion production at 500 kHz. Ultrasound Med. Biol. 6 (1), 38 (1980)
25. Clement GT, Hynynen K. A noninvasive method for focusing ultrasound through the human skull. Phys. Med. Biol. 47 (8), 1219 - 1236 (2002) .
26. Hynynen K, Vykhodtseva NI, Chung AH, Sorrentino V, Colucci V, Jolesz FA . Thermal effects of focused ultrasound on the brain: determination with MR imaging. Radiology 204 (1), 247 - 253 (1997) .
27. Clement GT, White PJ, King RL, McDannold N, Hynynen K. A magnetic resonance imaging-compatible, large-scale array for trans-skull ultrasound surgery and therapy. J. Ultrasound Med. 24 (8), 1117 - 1125 (2005) .
28. Lapchak PA . Recommendations and practices to optimize stroke therapy: developing effective translational research programs. Stroke doi:10.1007/s12975-012- 0209-2 (2013) (Epub ahead of print) .
29. Schäfer S, Kliner S, Klinghammer L et al . Infl uence of ultrasound operating parameters on ultrasound-induced thrombolysis in vitro . Ultrasound Med. Biol. 31 (6), 841 - 847 (2005) .
30. Meunier JM, Holland CK, Lindsell CJ, Shaw GJ . Duty cycle dependence of ultrasound enhanced thrombolysis in a human clot model. Ultrasound Med. Biol., 576-583 (2007) .
31. Wilhelm-Schwenkmezger T, Pittermann P, Zajonz K, Kempski O, Dieterich M, Nedelmann M. Therapeutic application of 20-kHz transcranial ultrasound in an embolic middle cerebral artery occlusion model in rats: safety concerns. Stroke, 1031-1035 (2007) .
32. Daffertshofer M, Huang Z, Fatar M et al . Effi cacy of sonothrombolysis in a rat model of embolic ischemic stroke. Neurosci. Lett. (1-3) , 115 - 119 (2004)
33. Rosenschein U, Furman V, Kerner E, Fabian I, Bernheim J, Eshel Y . Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results. Circulation 102 (2), 238 - 245 (2000) .
34. Frenkel V, Oberoi J, Stone MJ et al . Pulsed high-intensity focused ultrasound enhances thrombolysis in an in vitro model. Radiology 239 (1), 86 - 93 (2006) .
35. Stone MJ, Frenkel V, Dromi S et al . Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study. Thromb. Res. 121 (2), 193 - 202 (2007) .
36. Williams AR, Chater BV, Allen KA, Sherwood MR, Sanderson JH . Release of beta-thromboglobulin from human platelets by therapeutic intensities of ultrasound. Br. J. Haematol. 40 (1), 142 (1978) .
37. Kornowski R, Meltzer RS, Chernine A, Vered Z, Battler A . Does external ultrasound accelerate thrombolysis? Results from a rabbit model. Circulation 89 (1), 344 (1994) .
38. Poliachik SL, Chandler WL, Mourad PD et al . Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent. Ultrasound Med. Biol. 25 (6), 991 - 998 (1999) .
39. Hademenos GJ, Massoud TF . Biophysical mechanisms of stroke. Stroke 28 (10), 2067 - 2077 (1997) .
40. Marder VJ, Chute DJ, Starkman S et al . Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 37 (8), 2086 - 2093 (2006) .
41. Saguchi T, Onoue H, Urashima M, Ishibashi T, Abe T, Furuhata H . Effective and safe conditions of low-frequency transcranial ultrasonic thrombolysis for acute ischemic stroke: neurologic and histologic evaluation in a rat middle cerebral artery stroke model. Stroke 39 (3), 1007 - 1011 (2008) .
42. Culp WC, Flores R, Brown AT et al . Successful microbubble sonothrombolysis without tissue-type plasminogen activator in a rabbit model of acute ischemic stroke. Stroke 42 (8), 2280 - 2285 (2011) .
43. Flores R, Hennings LJ, Lowery JD, Brown AT, Culp WC . Microbubble-augmented ultrasound sonothrombolysis decreases intracranial hemorrhage in a rabbit model of acute ischemic stroke. Invest. Radiol. 419 - 424 (2011) .
44. Burgess A, Huang Y, Waspe AC et al . High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke. PLoS ONE 7 (8), e42311 (2012) .
45. Shimizu J, Fukuda T, Abe T et al . Ultrasound safety with midfrequency transcranial sonothrombolysis: preliminary study on normal macaca monkey brain. Ultrasound Med. Biol. 38 (6), 1040 - 1050 (2012) .
46. Culp WC, Erdem E, Roberson PK, Husain MM . Microbubble potentiated ultrasound as a method of stroke therapy in a pig model: preliminary fi ndings. J. Vasc. Interv. Radiol. 14 (11), 1433 - 1436 (2003) .
47. Alexandrov AV, Mikulik R, Ribo M et al . A pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perfl utren-lipid, microspheres for acute ischemic stroke. Stroke 39 (5), 1464 - 1469 (2008) .
48. Alexandrov AV, Molina CA, Grotta JC et al .; CLOTBUST Investigators . Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N. Engl. J. Med. 351 (21), 2170 - 2178 (2004) .
49. Molina CA, Barreto AD, Tsivgoulis G et al . Transcranial ultrasound in clinical sonothrombolysis (TUCSON) trial. Ann. Neurol. 66 (1), 28 - 38 (2009) .
50. Eggers J, König 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 39 (5), 1470 - 1475 (2008) .
51. Eggers J, Seidel G, Koch B, König IR . Sonothrombolysis in acute ischemic stroke for patients ineligible for rt-PA. Neurology,1052 - 1054 (2005).
52. Devcic-Kuhar B, Pfaffenberger S, Gherardini L et al . Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro . Thromb. Haemost. 92 (5), 980 - 985 (2004) .
53. Pfaffenberger S, Devcic-Kuhar B, El-Rabadi K et al . 2MHz ultrasound enhances tPA-mediated thrombolysis: comparison of continuous versus pulsed ultrasound and standing versus travelling acoustic waves. Thromb. Haemost. 89 (3), 589 (2003) .
54. Datta S, Coussios CC, Ammi AY, Mast TD, de Courten-Myers GM, Holland CK . Ultrasound-enhanced thrombolysis using Defi nity as a cavitation nucleation agent. Ultrasound Med. Biol. 34 (9), 1421 - 1433 (2008) .
55. Behrens S, Daffertshofer M, Spiegel D, Hennerici M . Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull. Ultrasound Med. Biol., 269 - 273 (1999) .
56. Holscher T, Raman R, Ernström K et al . In vitro sonothrombolysis with duplex ultrasound: fi rst results using a simplifi ed model. Cerebrovasc. Dis. 28 (4), 365 - 370 (2009) .
57. Alonso A, Dempfle CE, Della Martina A et al . In vivo clot lysis of human thrombus with intravenous abciximab immunobubbles and ultrasound. Thromb. Res., 70 - 74 (2009) .
58. Dijkmans PA, Juffermans LJ, Musters RJ et al . Microbubbles and ultrasound: from diagnosis to therapy. Eur. J. Echocardiogr., 245 - 256 (2004) .
59. Daffertshofer M, Gass A, Ringleb P et al . Transcranial low-frequency ultrasoundmediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a Phase II clinical trial. Stroke 36 (7), 1441 - 1446 (2005) .
60. Siegel RJ, Atar S, Fishbein MC et al . Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries. Echocardiography 18 (3), 247 - 257 (2001) .
61. STAIR. Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke, 2752 - 2758 (1999) .
62. Wang Z, Fukuda T, Azuma T, Furuhata H . Safety of low-frequency transcranial ultrasound in permanent middle cerebral artery occlusion in spontaneously hypertensive rats. Cerebrovasc. Dis. 33 (1), 23 - 29 (2012) .
63. Fatar M, Stroick M, Griebe M, Alonso A, Hennerici MG, Daffertshofer M . Brain temperature during 340-kHz pulsed ultrasound insonation: a safety study for sonothrombolysis. Stroke 37 (7), 1883 - 1887 (2006) .
64. Schneider F, Gerriets T, Walberer M et al . Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats. Stroke 37 (5), 1301 - 1306 (2006) .
65. Casals JB, Pieri NC, Feitosa ML et al . The use of animal models for stroke research: a review. C omp. Med. 61 (4), 305 - 313 (2011) .
66. Lapchak PA . Translational stroke research using a rabbit embolic stroke model: a correlative analysis hypothesis for novel therapy development. Transl. Stroke Res., 96 - 107 (2010) .
67. Turner RJ, Jickling GC, Sharp FR . Are underlying assumptions of current animal models of human stroke correct: from STAIRs to High Hurdles? Transl. Stroke Res. 2 (2), 138 - 143 (2011) .
68. Donnan GA . The 2007 Feinberg lecture: a new road map for neuroprotection. Stroke, 242 (2008) .
69. Tsivgoulis G, Eggers J, Ribo M et al . Safety and effi cacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke. 41 (2), 280 - 287 (2010) .
70. Ricci S, Dinia L, Del Sette M et al . Sonothrombolysis for acute ischaemic stroke. Cochrane Database Syst. Rev. 10, CD008348 (2012) .
71. Tsivgoulis G, Culp WC, Alexandrov AV . Ultrasound enhanced thrombolysis in acute arterial ischemia. Ultrasonics 48 (4), 311 (2008) .
72. Tsivgoulis G, Alexandrov AV . Ultrasound- enhanced thrombolysis in acute ischemic stroke: potential, failures, and safety. Neurotherapeutics 4 (3), 420 - 427 (2007) .
73. Meairs S, Alonso A, Hennerici MG . Progress in sonothrombolysis for the treatment of stroke. Stroke 43 (6), 1706 - 1710 (2012) .
74. Eggers J, Koch B, Meyer K, König I, Seidel G . Effect of ultrasound on thrombolysis of middle cerebral artery occlusion. Ann. Neurol. 53 (6), 797 - 800 (2003) .
75. Alexandrov AV, Wojner AW, Grotta JC; CLOTBUST Investigators . CLOTBUST: design of a randomized trial of ultrasoundenhanced thrombolysis for acute ischemic stroke. J. Neuroimaging 14 (2), 108 - 112 (2004) .
76. Saver JL . Improving reperfusion therapy for acute ischaemic stroke. J. Thromb. Haemost. 9 (Suppl. 1), 333 - 343 (2011) .
77. Baron C, Aubry JF, Tanter M, Meairs S, Fink M . Simulation of intracranial acoustic fi elds in clinical trials of sonothrombolysis. Ultrasound Med. Biol. 35 (7), 1148 - 1158 (2009) .
78. Kobayashi N, Yasu T, Yamada S et al . Infl uence of contrast ultrasonography with perfl utren lipid microspheres on microvessel injury. Circ. J. 67 (7), 630 - 636 (2003) .
79. Alexandrov AV, Tsivgoulis G, Rubiera M et al .; TUCSON Investigators . End-diastolic velocity increase predicts recanalization and neurological improvement in patients with ischemic stroke with proximal arterial occlusions receiving reperfusion therapies. Stroke 41 (5), 948 - 952 (2010) .
80. Barlinn K, Tsivgoulis G, Molina CA et al .; for the TUCSON Investigators . Exploratory analysis of estimated acoustic peak rarefaction pressure, recanalization, and outcome in the transcranial ultrasound in clinical sonothrombolysis trial. J. Clin. Ultrasound doi:10.1002/jcu.21978 (2012) (Epub ahead of print) .
81. Perren F, Loulidi J, Poglia D, Landis T, Sztajzel R . Microbubble potentiated transcranial duplex ultrasound enhances IV thrombolysis in acute stroke. J. Thromb. Thrombolysis 25 (2), 219 - 223 (2008) .
82. Hölscher T, Fisher DJ, Ahadi G, Voie A . Introduction of a rabbit carotid artery model for sonothrombolysis research. Transl. Stroke Res. 3 (3), 397 - 407 (2012) .
83. Meairs S, Culp W . Microbubbles for thrombolysis of acute ischemic stroke. Cerebrovasc. Dis. 27 (Suppl. 2), 55 - 65 (2009) .
84. Molina CA, Ribo M, Rubiera M et al . Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke 37 (2), 425 - 429 (2006) .
85. Borrelli MJ, O'Brien WD Jr, Hamilton E et al . Infl uences of microbubble diameter and ultrasonic parameters on in vitro sonothrombolysis effi cacy. J. Vasc. Interv. Radiol. 23 (12) , 1677 - 1684.e1 (2012) .
86. Leeman JE, Kim JS, Yu FT et al . Effect of acoustic conditions on microbubble-mediated microvascular sonothrombolysis. Ultrasound Med. Biol. 38 (9), 1589 - 1598 (2012) .
87. Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B . High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann. Neurol., 858 - 861 (2009) .
88. Damianou C, Ioannides K, Hadjisavvas V, Mylonas N, Couppis A, Iosif D . In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56 (6), 1189 - 1198 (2009) .
89. ter Haar GR . High intensity focused ultrasound for the treatment of tumors. Echocardiography 18 (4), 317 - 322 (2001) .
90. Jolesz FA, McDannold N . Current status and future potential of MRI-guided focused ultrasound surgery. J. Magn. Reson. Imaging 27 (2), 391 - 399 (2008) .
91. Maxwell AD, Cain CA, Duryea AP, Yuan L, Gurm HS, Xu Z . Noninvasive thrombolysis using pulsed ultrasound cavitation therapy - histotripsy. Ultrasound Med. Biol. 35 (12), 1982 - 1994 (2009) .
92. Spengos K, Behrens S, Daffertshofer M, Dempfl e CE, Hennerici M . Acceleration of thrombolysis with ultrasound through the cranium in a fl ow model. Ultrasound Med. Biol. 26 (5), 889 - 895 (2000) .
93. The World Health Report (2002). www.who.int/whr/2002/en/whr02-en.pdf
94. ClinicalTrials.gov. CLOTBUST Handsfree trial. http://clinicaltrials.gov/ ct2/show/ NCT01240356
95. ClinicalTrials.gov. CLOTBUST-ER trial. http://clinicaltrials.gov/ct2/ show/ NCT01098981
96. ClinicalTrials.gov. Sonothrombolysis Potentiated by Microbubbles for Acute Ischemic Stroke trial. http://clinicaltrials.gov/ct2/show/ NCT01678495