An ultrasound device designed to produce highly focused sound waves might one day be used to break up stroke-causing blood clots in the brain without surgery or drugs. So far, the system has only been tested on clots in test tubes and animals, but researchers aim to start human tests by the end of 2011.
Thilo Hoelscher, a neurologist at the University of California at San Diego, is attacking the clots with a device developed by Israeli ultrasound technology company InSightec. The device surrounds the head with an array of transducers that can focus ultrasound beams on a single spot in the brain without damaging the skull.
The technology is already being tested in patients to remove diseased brain tissue, but treating stroke will require a more delicate hand. Hoelscher and colleagues will need to prove that the device can break up a clot without damaging nearby brain tissue.
Strokes are the most common cause of long-term disability in the United States, and the third most common cause of death. Typically, they occur when a blood clot blocks an artery and prevents blood from flowing to the brain. The longer the clot remains, the more brain tissue dies, and the lower a person’s chance for survival. “Anything you can do that’s going to safely restore blood flow more quickly could have a lot of potential for societal, medical, and economic impact,” says Evan Unger, a radiologist at the University of Arizona who is not involved in the research.
Today, only two proven methods are in use to bust clots. A drug called tissue plasminogen activator (tPA) dissolves clots, but it can only be given to certain patients, and it usually must be administered within three hours of the stroke itself. Alternatively, some clots can be physically retrieved through a blood vessel, but few hospitals practice this technique. Overall, perhaps fewer than 10 percent of all patients are candidates for either of these interventions.
InSightec’s high-intensity focused ultrasound (HIFU) device is a bit like a helmet, lined with more than 1,000 ultrasound transducers. Each can be focused individually to send a beam into the brain of the person wearing the helmet. The focused beams converge on a spot only four millimeters wide, accurate enough to hit an artery-blocking clot and dissolve it in under a minute. “Outside this focus, the ultrasound energy is completely negligible,” Hoelscher says.
In studies in rabbits, Hoelscher and colleagues have shown that the InSightec system can break up clots in the brain without harming healthy tissue. Beyond animal studies, the researchers have shown that HIFU can focus on and break up blood clots in skulls of human cadavers–the sound waves are undeterred by bone, a tricky substance that absorbs energy and can alter a beam’s path.
“I’m enthusiastic, but cautiously enthusiastic,” says Robert Siegel, an ultrasound specialist and cardiologist at Cedars-Sinai Medical Center in Los Angeles. “In theory it should be doable, but the hurdles are large.” And, he notes, some major questions remain unanswered.
The first question is how radiologists will be able to pinpoint the clot’s exact location to precisely focus the beams. Researchers at the University of Virginia in Charlottesville are working to combine HIFU with magnetic resonance angiography to precisely locate blockages.
The second question is one of safety. “Heating the brain is not a good thing,” Siegel says. “Generally, we cool the brain to protect it. If you’re only using ultrasound, you’re relying on heat. And if you put heat into the skull, it can’t get out, and [it] could instead amplify.”
Hoelscher agrees, saying that his lab at UCSD is now looking into all of the related mechanisms. “We have to understand the skull bone, what it does with the ultrasound, how the ultrasound breaks up the blood clot, what happens with the tissue,” he says.
To make the technique even safer, Hoelscher is also looking to combine HIFU with another ultrasound method, one that works in conjunction with an intravenous contrast agent called Definity developed by the University of Arizona’s Unger. Typically used to increase contrast in heart sonograms, Definity consists of millions of tiny microbubbles that magnify sound waves. “They have the potential to function as little bombshells in the vicinity of a blood clot,” Hoelscher says. If microbubbles can amplify the effects of HIFU, he says, it may be possible to use less energy to break up clots, decreasing potential for brain tissue damage.