Focused Ultrasound Plus Microbubbles Enhances Glymphatic Transport in the Brain


Key Points

  • The research team led by Hong Chen, PhD, has published preclinical work showing that focused ultrasound plus microbubbles can enhance glymphatic clearance in the brain. 
  • This work has implications for treating stroke, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. 
  • There are currently no noninvasive ways to access the glymphatic system in humans. 
Glymphatic System
A microscopic image reveals the enhanced glymphatic transport of an intranasally delivered tracer (red), which was achieved using focused ultrasound combined with microbubbles. (Credit: Chen Lab)

Mechanically Manipulating Glymphatic Transport by Ultrasound Combined with Microbubbles 

The research team at Washington University in St. Louis (WUSTL) led by Hong Chen, PhD, recently published preclinical work using focused ultrasound plus microbubbles (FUSMB) to enhance the brain’s glymphatic clearance system. The work has implications for understanding how the brain clears waste and distributes molecules, which is especially important when studying stroke, Alzheimer’s disease, Parkinson’s disease, or other neurodegenerative disorders. 

The group found FUSMB to be a noninvasive, nonpharmaceutical way to influence glymphatic transport by intravenously or intranasally administering a fluorescent fluid tracer, injecting microbubbles intravenously, and sonicating the thalamus with focused ultrasound. They then compared FUSMB with a conventional technique for studying glymphatic transport. Advanced microscopic imaging showed that the FUSMB method could move the fluid tracer throughout the glymphatic system’s arterioles and other brain structures. 

The study’s lead author Dezhuang (Summer) Ye, PhD, led this work while completing her postdoctoral research. She was a 2022 recipient of the Foundation’s Young Investigator Awards and Bracco’s Women in Focused Ultrasound Award. 

“Regardless of whether tracers were delivered via the intranasal or injected route, FUSMB consistently improved glymphatic transport,” said Ye, in the WUSTL press release. “Our study using confocal microscopy imaging combined with brain-tissue clearing obtained direct evidence that unequivocally proved that FUSMB enhanced the glymphatic transport of a labeled protein agent in mice.” 

Dr. Chen added, “Intranasal delivery provides a novel, noninvasive route to investigate the glymphatic pathway in intact brains…This route for investigating glymphatic transport has the potential to be utilized in the study of glymphatic function in humans, which is currently limited by the absence of noninvasive approaches to access the glymphatic system.” 

See Proceedings of the National Academy of Sciences (PNAS)  (Open Access) 

See the Washington University in St. Louis Press Release  

See media coverage in Neuroscience News and Aunt Minnie 

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