Sonothrombolysis, also known as ultrasound-enhanced thrombolysis, employs ultrasound energy as an adjunct therapy to speed and improve the effectiveness of clot-busting drugs.
Transcranial ultrasound supplements use of the drug tPA (tissue plasminogen activator), which is usually administered within hours of an ischemic stroke. Andrei Alexandrov, a professor of Neurology, director of the Comprehensive Stroke Center at the University of Alabama at Birmingham and a Wake Forest School of Medicine Program of Medical Ultrasound guest faculty member, has been a leading investigator of the technique. Alexandrov initially used ultrasound to track the efficacy of tPA and discovered that patients being monitored with ultrasound were recovering faster than those who were not.
A subsequent study, CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA), confirmed that ultrasound improved the clot-dissolving ability of tPA. When used alone, tPA completely breaks up about 13 percent of clots; adding ultrasound raises the success rate to 38 percent. Introducing microspheres, tiny gas-filled bubbles that explode in the clot when ultrasound waves strike them, further improves the ability of tPA to penetrate and dissolve clots.
Alexandrov later outfitted patients with a sort of helmet that held the ultrasound transducer in place while patients received the drug. The device delivered therapeutic ultrasound to the target region without the need to aim the transducer or hold it by hand for long periods. Cerevast Therapeutics, a privately held medical technology company based in Redmond, Wash., has commercialized the approach with its Clotbust ER™, a sonolysis headframe system with multiple transducers that self-align to the patient’s skull. Its operator-independent design enables rapid treatment in the emergency room setting after a stroke patient arrives.
To treat deep vein thrombosis (DVT), a catheter inserted into the affected vein delivers both ultrasonic energy and a lytic agent directly to the clot. EKOS Corp. is a leader in this therapy.
Read more about EKOS.
Drug Delivery and Gene Therapy
In the same way that ultrasound helps drugs penetrate blood clots, ultrasonic energy is being adapted to enhance the uptake of drugs by tissues, to improve the delivery of drugs and genetic material to specific targeted sites, and to deliver chemotherapeutic drugs into tumors while minimizing toxicity to other parts of the body.
Ultrasonic transdermal delivery of insulin has received the most attention, but hormones, steroids and antigens for vaccination potentially could be delivered transdermally. Ultrasound can increase drug absorption as much as tenfold by heating up skin tissues and making cell membranes more permeable. Various small ultrasound transducers have been proposed, including a piston-shaped device with an insulin reservoir, one designed to be worn as a patch, and even a pill that would release the drug, send ultrasound wave through the patient’s gastrointestinal tracts and then pass through the digestive system as a camera pills does. Recent studies have found that combining two separate ultrasound beams, one of low frequency and another of high frequency, is more effective than a single frequency.
Another ultrasonically activated drug delivery approach employs microbubbles similar to those found in contrast agents but carrying drugs rather than simply gas. Ultrasonic cavitation shears the bubbles, releasing their therapeutic contents at the specific site where the ultrasound is applied. Ongoing research must address the optimal bubble sizes and ultrasonic frequencies for efficient drug delivery without causing mechanical or thermal damage to tissues. Those findings could require a new generation of transducers, perhaps even multi-frequency devices capable of imaging a target, increasing cell membrane permeability and collapsing the bubbles, all at different frequencies.
Willam G. Pitt, Ghaleb A. Hesseini, and Bryant J. Staples, “Ultrasonic Drug Delivery—A General Review,” Expert Opinion on Drug Delivery 1 no. 1, November 2004.
Will Ferguson, “Ultrasound Pill Helps the Medicine Go Down,” New Scientist, June 25, 2012.
The Whitaker Foundation, “New Ultrasound Insulin Patch Could Eliminate Needles, November 11, 2002.
Osama M Al-Bataineh, Khaldon Lweesy, and Luay Fraiwan, “Noninvasive Transdermal Insulin Delivery Using Pistion-Shaped PZT Transducers: In vivo Rabbits Evaluation,” Jordan Journal of Mechanical and Industrial Engineering 5, no. 1, February 2012, 11-16.
Anne Trafton, “Getting (Drugs) Under Your Skin,” MIT News Office, September 13, 2012.