Transcranial sonothrombolysis using high-intensity focused ultrasound: impact of increasing output power on clot fragmentation

Journal of Therapeutic Ultrasound

Thilo Hölscher⁵  Arne H Voie¹  Karin Ernström²  Eyal Zadicario³  David J Fisher¹  Michele J Grimm⁴  Christian S Welch¹  Golnaz Ahadi⁴ 

[1] Department of Radiology, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103-8756, USA;Department of Family and Preventive Medicine, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103-8756, USA;Neuro Program, InSightec, Inc., Tirat Carmel, Israel;Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, USA;Department of Neurosciences, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103-8756, USA

关键词: Clot debris;    Clot fragmentation;    Stroke;    High-intensity focused ultrasound;    Thrombolysis;   

Others  :  801320
DOI  :  10.1186/2050-5736-1-22

 received in 2013-05-08, accepted in 2013-08-13,  发布年份 2013

【 摘 要 】

Background

The primary goal of this study was to investigate the relationship between increasing output power levels and clot fragmentation during high-intensity focused ultrasound (HIFU)-induced thrombolysis.

Methods

A HIFU headsystem, designed for brain applications in humans, was used for this project. A human calvarium was mounted inside the water-filled hemispheric transducer. Artificial thrombi were placed inside the skull and located at the natural focus point of the transducer. Clots were exposed to a range of acoustic output power levels from 0 to 400 W. The other HIFU operating parameters remained constant. To assess clot fragmentation, three filters of different mesh pore sizes were used. To assess sonothrombolysis efficacy, the clot weight loss was measured.

Results

No evidence of increasing clot fragmentation was found with increasing acoustic intensities in the majority of the study groups of less than 400 W. Increasing clot lysis could be observed with increasing acoustic output powers.

Conclusion

Transcranial sonothrombolysis could be achieved in vitro within seconds in the absence of tPA and without producing relevant clot fragmentation, using acoustic output powers of <400 W.

【 授权许可】

   
2013 Ahadi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Dumont TM, Mokin M, Sorkin GC, Levy EI: Siddiqui AH. Journal of Neurointerventional Surgery: Aspiration thrombectomy in concert with stent thrombectomy; 2013. doi:10.1136/neurintsurg-2012-010624.rep.
• [2]Marder VJ, Chute DJ, Starkman S, Abolian AM, Kidwell C, Liebeskind D, Ovbiagele B, Vinuela F, Duckwiler G, Jahan R, Vespa PM, Selco S, Rajajee V, Kim D, Sanossian N, Saver JL: Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 2006, 37(8):2086-93. doi:10.1161/01.STR.0000230307.03438.94.
• [3]Prokop AF, Soltani A, Roy RA: Cavitational mechanisms in ultrasound-accelerated fibrinolysis. Ultrasound Med Biol 2007, 33(6):924-33.
• [4]Braaten JV, Goss RA, Francis CW: Ultrasound reversibly disaggregates fibrin fibers. Thromb Haemost 1997, 78(3):1063-68.
• [5]Devcic-Kuhar B, Pfaffenberger S, Gherardini L, Mayer C, Groschl M, Kaun C, Benes E, Tschachler E, Huber K, Maurer G, Wojta J, Gottsauner-Wolf M: Ultrasound affects distribution of plasminogen and tissue-type plasminogen activator in whole blood clots in vitro. Thromb Haemost 2004, 92(5):980-85.
• [6]Datta S, Ammi AY, Coussios CC, Holland CK: Monitoring and simulating stable cavitation during ultrasound-enhanced thrombolysis. J Acoust Soc Am 2007, 122(3052):3052-52.
• [7]Datta S, Coussios CC, McAdory LE, Tan J, Porter T, De Courten-Myers G, Holland CK: Correlation of cavitation with ultrasound enhancement of thrombolysis. Ultrasound Med Biol 2006, 32(8):1257-67. doi:10.1016/j.ultrasmedbio.2006.04.008.
• [8]Hitchcock KE, Ivancevich NM, Haworth KJ, Caudell Stamper DN, Vela DC, Sutton JT, Pyne-Geithman GJ, Holland CK: Ultrasound-enhanced rt-PA thrombolysis in an ex vivo porcine carotid artery model. Ultrasound Med Biol 2011, 37(8):1240-51.
• [9]Alexandrov AV, Mikulik R, Ribo M, Sharma VK, Lao AY, Tsivgoulis G, Sugg RM, Barreto A, Sierzenski P, Malkoff MD, Grotta JC: A pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perflutren-lipid microspheres for acute ischemic stroke. Stroke 2008, 39(5):1464-69.
• [10]Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moyé LA, Hill MD, Wojner AW, CLOTBUST Investigators: Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004, 351(21):2170-78.
• [11]Eggers J, Koch B, Meyer K, Konig I, Seidel G: Effect of ultrasound on thrombolysis of middle cerebral artery occlusion. Ann Neurol 2003, 53(6):797-800.
• [12]Eggers J, Konig IR, Koch B, Handler 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(5):1470-75.
• [13]Alonso A, Dempfle CE, Della Martina A, Stroick M, Fatar M, Zohsel K, Allémann E, Hennerici MG, Meairs S: In vivo clot lysis of human thrombus with intravenous abciximab immunobubbles and ultrasound. Thromb Res 2009, 124(1):70-4.
• [14]Meunier JM, Holland CK, Lindsell CJ, Shaw GJ: Duty cycle dependence of ultrasound enhanced thrombolysis in a human clot model. Ultrasound Med Biol 2007, 33(4):576-83.
• [15]Meairs S, Culp W: Microbubbles for thrombolysis of acute ischemic stroke. Cerebrovasc Dis 2009, 27(Suppl 2):55-65.
• [16]Porter TR, LeVeen RF, Fox R, Kricsfeld A, Xie F: Thrombolytic enhancement with perfluorocarbon-exposed sonicated dextrose albumin microbubbles. Am Heart J 1996, 132(5):964-68.
• [17]Pieters M, Hekkenberg RT, Barrett-Bergshoeff M, Rijken DC: The effect of 40 kHz ultrasound on tissue plasminogen activator-induced clot lysis in three in vitro models. Ultrasound Med Biol 2004, 30(11):1545-52.
• [18]Greenberg RK, Ouriel K, Srivastava S, Shortell C, Ivancev K, Waldman D, Illig K, Green R: Mechanical versus chemical thrombolysis: an in vitro differentiation of thrombolytic mechanisms. J Vasc Interv Radiol 2000, 11(2 Pt 1):199-205.
• [19]Hartnell GG, Saxton JM, Friedl SE, Abela GS, Rosenschein U: Ultrasonic thrombus ablation: in vitro assessment of a novel device for intracoronary use. J Interv Cardiol 1993, 6(1):69-76.
• [20]Rosenschein U, Furman V, Kerner E, Fabian I, Bernheim J, Eshel Y: Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results. Circulation 2000, 102(2):238-45.
• [21]Wright C, Hynynen K: Goertz D. Invest Radiol: In vitro and in vivo high-intensity focused ultrasound thrombolysis; 2012. doi:10.1097/RLI.0b013e31823cc75c.
• [22]Holscher T, Fisher D, Raman R, Ernstrom K, Zadicario E, Bradley W: Voie A. Journal of Neurology and Neurophysiology: Noninvasive transcranial clot lysis using high intensity focused ultrasound; 2011. doi:10.4172/2155-9562.S1-002.
• [23]Moody DM, Brown WR, Challa VR, Stump DA, Reboussin DM, Legault C: Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg 1995, 59(5):1304-07.
• [24]Hudetz AG: Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy. Microcirculation 1997, 4(2):233-52.
• [25]Kulik T, Kusano Y, Aronhime S, Sandler AL, Winn HR: Regulation of cerebral vasculature in normal and ischemic brain. Neuropharmacology 2008, 55(3):281-88.
• [26]Wright CC, Hynynen K, Goertz DE: Pulsed focused ultrasound-induced displacements in confined in vitro blood clots. IEEE Trans Biomed Eng 2012, 59(3):842-51. doi:10.1109/TBME.2011.2180904.
• [27]Maxwell AD, Cain CA, Duryea AP, Yuan L, Gurm HS, Xu Z: Noninvasive thrombolysis using pulsed ultrasound cavitation therapy - histotripsy. Ultrasound Med Biol 2009, 35(12):1982-94.
• [28]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(7):1441-46.
• [29]Kennedy JE, Ter Haar GR, Cranston D: High intensity focused ultrasound: surgery of the future? Br J Radiol 2003, 76(909):590-99.