Focused Ultrasound Clears Metabolic Waste from the Brain

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Key Points

  • Although a vital brain function, metabolic waste clearance is disrupted in many neurological diseases. 
  • Researchers recently studied the use of focused ultrasound to clear solutes from the brain.
  • The technique could be used to treat Alzheimer’s disease, traumatic brain injury, hydrocephalus, and stroke.
Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound.
Image source: Yoo, SS., Kim, E., Kowsari, K. et al. Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound. Sci Rep 13, 12339 (2023). https://doi.org/10.1038/s41598-023-39640-2

Non-Invasive Enhancement of Intracortical Solute Clearance Using Transcranial Focused Ultrasound 

Seung-Schik Yoo, PhD, and his team in the Neuromodulation and Tissue Engineering Laboratory in the Department of Radiology at Brigham and Women’s Hospital and Harvard University once again collaborated with colleagues from Kyungpook National University and Yonsei University in the Republic of Korea to conduct a preclinical study showing how focused ultrasound can noninvasively assist with solute clearance in the brain, all without disrupting the blood-brain barrier. 

Because their previous studies showed that focused ultrasound could enhance the transport of cerebrospinal fluid (CSF) in the brain, the group sought to determine whether the technology could also enhance the transport and clearance of solutes injected into the cortex of the brain. If successful, the technique could be developed for the treatment of various disorders that are implicated with aberrant brain waste clearance, for example, Alzheimer’s disease, traumatic brain injury, hydrocephalus, and stroke. 

After injecting fluorescent ovalbumin and high molecular-weight dextran into the cortex of rat brains, the team applied its previously determined protocol of pulsed, low-intensity focused ultrasound to help transport the molecules from the cortex into the parenchyma. When compared with the control group, the focused ultrasound produced 34.6% to 40.1% greater parenchymal tracer volume plus 78.3% higher drainage of the interstitial ovalbumin to the superficial and deep cervical lymph nodes on the side opposite the sonication. The team did not use microbubbles, which are known to disrupt the blood-brain barrier. 

“We are continuing our work with this line of studies because of its great potential to be translated to human medicine,” said Dr. Yoo. “There are many neurological conditions that could benefit from a treatment that clears waste from the brain. Our next step is to apply the technology to promote the preemptive removal of amyloid beta oligomers and protofibrils from the brain through animal models of Alzheimer’s disease. Since the technique does not involve intentional opening of blood-brain barrier, it would favor the repeated routine applications.” 

The study concluded that a noninvasive focused ultrasound treatment could potentially offer a nonpharmacological way to clear undesirable metabolic waste from the brain. Although a vital brain function, waste clearance is disrupted in many neurological diseases. 

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