Abstract
Clinically available thrombolysis techniques are limited by either slow reperfusion
(drugs) or invasiveness (catheters) and carry significant risks of bleeding. In this
study, the feasibility of using histotripsy as an efficient and noninvasive thrombolysis
technique was investigated. Histotripsy fractionates soft tissue through controlled
cavitation using focused, short, high-intensity ultrasound pulses. In vitro blood clots formed from fresh canine blood were treated by histotripsy. The treatment
was applied using a focused 1-MHz transducer, with five-cycle pulses at a pulse repetition
rate of 1 kHz. Acoustic pressures varying from 2 to 12 MPa peak negative pressure were tested. Our results show that histotripsy can perform
effective thrombolysis with ultrasound energy alone. Histotripsy thrombolysis only
occurred at peak negative pressure ≥6 MPa when initiation of a cavitating bubble cloud was detected using acoustic backscatter
monitoring. Blood clots weighing 330 mg were completely broken down by histotripsy in 1.5 to 5 min. The clot was fractionated to debris with >96% weight smaller than 5 μm diameter. Histotripsy thrombolysis treatment remained effective under a fast, pulsating
flow (a circulatory model) as well as in static saline. Additionally, we observed
that fluid flow generated by a cavitation cloud can attract, trap and further break
down clot fragments. This phenomenon may provide a noninvasive method to filter and
eliminate hazardous emboli during thrombolysis. (E-mail: [email protected])
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Ultrasound in Medicine and BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Catheter-directed thrombolysis (intrathrombus injection) in treatment of deep venous thrombosis: A systematic review.Catheter Cardio Intervent. 2007; 70: 143-148
- Cavitation cluster dynamics in shock-wave lithotripsy: Part 1. Free field.Ultrasound Med Biol. 2005; 31: 827-839
- Perspectives on the role of ultrasonic devices in thrombolysis.J. Thromb. Thrombolys. 2004; 17: 107-114
- Treatment of deep-vein thrombosis.N Engl J Med. 2004; 351: 268-277
- Iliofemoral deep venous thrombosis: Safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy.J Vasc Intervent Radiol. 1997; 8: 405-418
- Jet formation and shock wave emission during collapse of ultrasound-induced cavitation bubbles and their role in the therapeutic applications of high-intensity focused ultrasound.Phys Med Biol. 2005; 50: 4797-4809
- Controlled ultrasound tissue erosion: The effects of tissue type, exposure parameters and the role of dynamic microbubble activity.IEEE Ultrason Symp. 2004; 3: 1808-1811
- Robbins pathologic basis of disease.7th edition. W.B. Saunders Co., Philadelphia, PA1999
- Ultrasonic investigations of hemolysis.Ultrasound Med Biol. 1977; 2: 339-341
- Damage to red blood cells induced by acoustic cavitation.Ultrasound Med Biol. 1995; 21: 113-119
- BSAVA manual of canine and feline haematology and transfusion medicine.British Small Animal Veterinary Association, Quedgeley, Gloucester, UK2000
- In vitro measurements of inertial cavitation thresholds in human blood.Ultrasound Med Biol. 1996; 22: 939-948
- Cavitation microstreaming.J Acoust Soc Am. 1959; 31: 54-64
- Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy.J Urol. 2002; 168: 1556-1562
- Ultrasound and thrombolysis.Vasc Med. 2001; 6: 181-187
- Prophylaxis and treatment of deep vein thrombosis in general surgery.Am J Surg. 2005; 189: 14-22
- A real-time measure of cavitation induced tissue disruption by ultrasound imaging backscatter reduction.IEEE Trans Ultrason Ferroelectr Freq Control. 2007; 54: 569-575
- On the dynamics of cavity clusters.J Phys D Appl Phys. 1982; 15: 1725-1734
- Physical properties of tissues relevant to arterial ultrasound imaging and blood velocity measurement.Ultrasound Med Biol. 2007; 33: 1527-1539
- Cloud cavitation control for lithotripsy using high intensity focused ultrasound.Ultrasound Med Biol. 2006; 32: 1383-1397
- Refining Histotripsy: Defining the parameter space for the creation of nonthermal lesions with high-intensity, pulsed focused ultrasound of the in vitro kidney.J Urol. 2007; 178: 672-676
- Catheter-directed thrombolysis with percutaneous rheolytic thrombectomy vs. thrombolysis alone in upper and lower extremity deep vein thrombosis.Cardiovasc Intervent Radiol. 2006; 29: 1003-1007
- Deep vein thrombosis.Lancet. 2005; 365: 1163-1174
- Acoustic microscopy: Fundamentals and applications.Wiley-VCH, Weinheim, Germany2008
- Catheter-directed thrombolysis for lower extremity deep venous thrombosis: Report of a national multicenter registry.Radiology. 1999; 211: 39-49
- A clinical perspective of venous thromboembolism.Arterioscler Thromb Vasc Biol. 2008; 28: 373-379
- Diagnostic yield of color Doppler ultrasonography in deep vein thrombosis.J Coll Physicians Surg Pak. 2005; 15: 276-279
- Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro.J Ultrasound Med. 2002; 21: 649-656
- Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis catheter.J Vasc Intervent Radiol. 2007; 18: 715-724
- Pulsed cavitational ultrasound therapy for controlled tissue homogenization.Ultrasound Med Biol. 2006; 32: 115-129
- Cost-effective assembly of a basic fiber-optic hydrophone for measurement of high-amplitude therapeutic ultrasound fields.J. Acoust Soc Am. 2006; 119: 1432-1440
- Spatial variability in acoustic backscatter as an indicator of tissue homogenate production in pulsed cavitational ultrasound therapy.IEEE Trans Ultrason Ferroelectr Freq Control. 2007; 54: 576-590
- Detection of significant variation in acoustic output of an electromagnetic lithotripter.J Urol. 2006; 176: 2294-2298
- Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent.Ultrasound Med Biol. 1999; 25: 991-998
- The relation between cavitation and platelet aggregation during exposure to high-intensity focused ultrasound.Ultrasound Med Biol. 2004; 30: 261-269
- Pulsed cavitational ultrasound: A noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney.J Urol. 2006; 175: 734-738
- Ultrasound imaging-guided noninvasive ultrasound thrombolysis: Preclinical results.Circulation. 2000; 102: 238-245
- Endovascular management of venous thrombotic and occlusive diseases of the lower extremities.J. Vasc Intervent Radiol. 2003; 14: 405-423
- Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries.Echocardiography. 2001; 18: 247-257
- Hemolytic reactions mechanically induced by kinked hemodialysis lines.Am J Kidney Dis. 1996; 27: 262-266
- In vivo whole-field blood velocity measurement techniques.Exp Fluids. 2007; 42: 495-511
- Effect of externally applied focused acoustic energy on clot disruption in vitro.Clin Sci. 1999; 97: 67-71
- Molecular imaging of human thrombus with computed tomography.Acad Radiol. 2005; 12: S9-S13
- Controlled ultrasound tissue erosion.IEEE Trans Ultrason Ferroelectr Freq Control. 2004; 51: 726-736
- Controlled ultrasound tissue erosion: The role of dynamic interaction between insonation and microbubble activity.J Acoust Soc Am. 2005; 117: 424-435
- A new strategy to enhance cavitational tissue erosion by using a high intensity initiating sequence.IEEE Trans Ultrason Ferroelectr Freq Control. 2006; 53: 1412-1424
- Effects of acoustic parameters on bubble cloud dynamics in ultrasound tissue erosion (histotripsy).J Acoust Soc Am. 2007; 122: 229-236
- Evolution of bubble clouds induced by pulsed cavitational ultrasound therapy-histotripsy.IEEE Trans Ultrason Ferroelectr Freq Control. 2008; 55: 1122-1132
- High-resolution MRI characterization of human thrombus using a novel fibrin-targeted paramagnetic nanoparticle contrast agent.Magn Reson Med. 2000; 44: 867-872
Article info
Publication history
Published online: October 26, 2009
Accepted:
July 7,
2009
Received in revised form:
May 24,
2009
Received:
October 9,
2008
Identification
Copyright
© 2009 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.