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Posted on Nov 25, 2019, 2 p.m.

Researchers from Stanford Medicine have developed an ultrasonic brain beam surgery that could extend life that is ready for human testing; the ultrasound method is nano-targeted delivery of drugs to specific brain regions.

The brain is the most complex organ in the body, it is wondrous and resilient, but it is also the most delicate organ in the body, leaving neuroscientists with limited tool to navigate the brain and treat its illnesses. 

One could cut it open before slicing or removing portions, or even implant electrodes, but such methods are highly invasive; less brutal routes are the safer way to break into a brain, these less invasive technologies are where nanoparticles come into play that are steered by magnetism and are growing in sophistication to show much promise. 

Being able to tackle neurological disorders linked to aging non-invasively could extend lifespans by many healthy years. However, one of the problems with magnetic steering of nanoparticles is that the process unfortunately often proves to be imprecise, which not many want to hear as a possibility before undergoing surgery on the most precious brain.

Raag Airan and colleagues from Stanford University suggest to have demonstrated a new nanotechnology driven non-invasive method for brain treatment that could open new paths to negate the challenges of treating the delicate brain. 

Their earlier findings were published last year in Neuron, since then the team has been working on further developing their technology and suggest that it is at the necessary level of precision, which has been tested successfully in rats. Nanoparticles were injected into “cages” which carry drugs into the bloodstream, which were tracked to the target site, upon arrival a beam of focused ultrasound is applied to release the drugs at the desired location which then cross the blood brain barrier to directly target brain function precisely where needed. 

Intensity of the ultrasound used was 1/10th to 1/100th the intensity used in clinical ablation procedures which was delivered in a series of short staccato pulses separated by periods of rest to allow the targeted area time to cool off between pulses. 

Each nanoparticle enclosed a droplet of perfluorocarbon which shake and expand when buffeted by ultrasound waves until the copolymer matrix coating surface ruptures to release the drug molecules. The anaesthetic propofol was used, effects were measured to be limited within a three millimetre volume determined by the beam focus; the method was used to anaesthetise the visual cortices of the animals while flashing lights in their eyes. The method was observed to be successful in reduced region specific brain activity while the beam was turned on; brain activity quickly returned within 10 seconds after the beam was turned off and the anaesthetic wore off. 

Applications for this technology go beyond anesthesia, drugs could be engineered for delivery using this method including those designed to combat cancer or mental illness. This approach also provides hope that it could be applied to mapping brain interconnectivity; finding and piecing together parts of the brain’s unknown jigsaw that fit together could prove to be a powerful way to predict wider consequences of removing parts, especially in the case of neurosurgery such as those designed to treat epilepsy, not just test for desired effect but also map potential side effects. 

"This important work establishes that ultrasonic drug uncaging appears to have the required precision to tune the brain's activity via targeted drug application," said Deisseroth, who wasn't involved in the study. "The powerful new technique could be used to test optogenetically inspired ideas, derived initially from rodent studies, in large animals -- and perhaps soon in clinical trials."

"We hope to use this technology to noninvasively predict the results of excising or inactivating a particular small volume of brain tissue in patients slated for neurosurgery," said Airan. "Will inactivating or removing that small piece of tissue achieve the desired effect -- for example, stopping epileptic seizure activity? Will it cause any unexpected side effects?"

The promising technology is still in early stages but the team is confident about the translational potential, “While this study was done in rats, each component of our nanoparticle complex has been approved for at least investigational human use by the Food and Drug Administration, and focused ultrasound is commonly employed in clinical procedures at Stanford,” said Airan. “So, we’re optimistic.”

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This article is not intended to provide medical diagnosis, advice, treatment, or endorsement.

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