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.