Neuroscientists have limited tools for understanding the human brain and treating its illnesses. Surgery or inserted electrodes are too invasive for most situations. Existing noninvasive technology, such as magnetic stimulation, is imprecise. Now neuroradiologist Raag Airan of Stanford University and his colleagues have demonstrated a method that could enable researchers to manipulate small, highly targeted brain areas noninvasively.
The study, published last November in Neuron, uses technology Airan has been developing for years—but this is the first time it has been shown to work with the necessary precision. The technique involves injecting nanoparticle “cages” filled with drug molecules into the bloodstream. Researchers then use a focused ultrasound beam to shake the drug particles loose from their cages in the desired location. There they cross the blood-brain barrier (a membrane between arteries and the brain that admits only tiny molecules), directly affecting brain function in only that spot.
Results from experiments in rats showed the action of the drug—an anesthetic—was limited to a three-millimeter cube where the beam was focused. The scientists aimed the ultrasound at the rats' visual cortices while flashing light in their eyes. Brain activity in the targeted region dropped when the beam was switched on, then recovered within 10 seconds after stimulation stopped, as the anesthetic wore off. “A spatially and temporally precise technology that allows us to intervene very focally in the brain is a tremendous goal,” says neurosurgeon Nir Lipsman of Sunnybrook Research Institute in Toronto, who was not involved in the study. The team also saw metabolic activity reduced in distant parts of the brain connected to target areas, suggesting the method could be used to map brain circuitry.
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The researchers found no evidence of tissue damage from the procedure. “They did a good job of demonstrating safety,” Lipsman says. The study is only a proof-of-concept, but Airan says translation to clinical use should be rapid. Ultrasound is already commonly used in medicine, and the nanoparticles are made from chemicals routinely used in radiology and cancer treatment. “We just have to show their combination isn't unsafe,” Airan says. “We're talking a first-in-human trial within a year or two.”
Next up: testing whether the technology can simulate the effects of planned neurosurgeries, by anesthetizing the surgical target area to confirm it can be disabled safely. The approach could also be used to deliver psychiatric drugs to specific brain areas, potentially reducing side effects and improving efficacy. “The mind boggles with the range of possibilities,” Airan says.
