Key Points
- Researchers developed and tested a new noninvasive focused ultrasound protocol for ultrasonic debris clearance (UDC) in the brain.
- UDC decreased inflammation, increased functional recovery, and improved survival in two preclinical models of stroke.
When neurotoxins – including blood cells from hemorrhage – accumulate in the brain, the neurons become damaged, resulting in the development of disease and loss of function. Symptoms of neurotoxicity include loss of coordination or balance, headache or other types of pain, and speech or vision problems. Diseases that arise from neurotoxins include Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS).
The research team led by Raag Airan, MD, PhD, assistant professor of neuroradiology at Stanford University, recently developed and tested a new noninvasive focused ultrasound protocol for clearing debris from the brain. Calling the technique “ultrasonic debris clearance,” or UDC, the group plans to translate their results into human clinical trials for stroke, traumatic brain injury, and neurodegenerative conditions.
After developing the UDC protocol, the team tested it in two preclinical models of brain bleeding. The protocol was effective at clearing debris from both the cerebrospinal fluid and the interstitium (the space between the cells). They hypothesized that the mechanism behind how UDC works is that the ultrasound energy activates a molecular mediator in the mechanically sensitive ion channels in the cells of these brain tissues. Importantly, they found that clearing debris with UDC decreased inflammation, increased function, and improved survival.
“I am continually impressed by how robust these effects proved to be,” said Dr. Airan. “Impressively, survival improved by 30% after only three 10-minute applications using this noninvasive protocol. If these results translate to humans, this research has implications beyond stroke – for neurodegenerative diseases and other conditions where inflammation and debris clearance could play a central role.”
During the studies, UDC was applied with a focused ultrasound system developed in the Airan Laboratory. The protocol met US Food and Drug Administration safety guidelines, however, so clinical translation should be feasible. For future experiments, the team is building an ultrasound helmet for human application. After all approvals are received, the helmet will be tested in Stanford’s memory disorders clinic in a clinical trial funded by Stanford’s Knight Initiative for Brain Resilience.
The preclinical work was funded by the Stanford Wu Tsai Neurosciences Institute, the National Institutes of Health (NIH) BRAIN Initiative, NIH HEAL Initiative, and other NIH grants, the Focused Ultrasound Foundation, an anonymous donor to the Stanford School of Medicine Radiology Department, the Ford Foundation, the National Science Foundation, the Hydrocephalus Association, the Shurl and Kay Curci Foundation, and a Complete Genomics Spatial Biology Grant.