Focused ultrasound waves can make a tiny, temporary hole in the barrier surrounding the brain.
Light spot on the right of image shows the blood-brain barrier opening as focused ultrasound is targeted toward the mouse’s right hippocampus. (Courtesy of James Choi and Elisa Konofagou.)
One of the biggest challenges in treating neurological conditions such as
Parkinson's and Alzheimer's disease is finding safe and non-invasive ways to enable drugs to penetrate the brain's natural defense -- the blood-brain barrier.
Now scientists have developed a way to temporarily open a very small part of that barrier using focused ultrasound. They hope this precise targeting will allow drugs to enter specific parts of the brain -- without exposing the rest of the brain and without damaging the barrier or surrounding neuronal tissue in the process.
Magnetic resonance imaging cross-section of mouse brain.
In work presented at the annual meeting of the Acoustic Society of America in Providence, RI, earlier this month, researchers from Columbia University used magnetic resonance imaging to reveal how the hippocampus can be targeted with focused ultrasound, without effecting the rest of the brain, in mice genetically engineered to have Alzheimer's disease. "The hippocampus is the region of the brain that controls the memory, among other things, and is the main region affected by Alzheimer's and Parkinson's," says Elisa Konofagou, assistant professor in biomedical engineering at Columbia University, who carried out the work.
Mouse brain with intact blood-brain barrier when exposed to low levels of focused ultrasound.
Using ultrasound in this way is a "huge deal," says Al Kyle, president and CEO of Perfusion Technology, a startup medical research company in Boston that's trying to develop similar technology. There are ways to open the blood-brain barrier using drugs, he says, "but it's a really harsh treatment and requires several days in clinical care." With more than 11 million people suffering from neurological diseases in the United States alone, says Kyle, a safer and less severe option is needed.
Light spot (on right) shows the blood-brain barrier opening as focused ultrasound is targeted toward the mouse’s right hippocampu
Research by Kullervo Hynynen at the University of Toronto, which first demonstrated the potential use of ultrasound to open the barrier in 2001, has suggested that using ultrasound to open the blood-brain barrier is safe. But Hynynen is still cautious about the applications for this use of ultrasound. "There could be significant clinical potential," he says, but adds that it won't be certain until someone does it in humans.
Light regions (on lower right) show a contrast agent diffusing into the right hippocampus, demonstrating how focused ultrasound could be used for drug delivery.
The blood-brain barrier protects the brain, which is why it can be difficult for drugs to penetrate it. The barrier consists of endothelial cells that line the small blood vessels in the brain. These cells are tightly packed to create a wall between most parts of the brain and the rest of the circulatory system, blocking bacteria and all but the smallest molecules.