Focused Ultrasound Improves Liquid Biopsy Results in an Alzheimer’s Disease Model

Hong Chen, PhD, her co-senior author Arash Nazeri, MD, an assistant professor of radiology at the School of Medicine’s Mallinckrodt Institute of Radiology, and their research team at Washington University in St. Louis (WUSTL), recently completed a preclinical study using focused ultrasound–mediated liquid biopsy (sonobiopsy) to improve the quantity of biomarkers released from specific regions of the brain into the blood in a model of Alzheimer’s disease.

The blood-brain barrier (BBB) limits the flow of biomarkers from the brain into the blood. Using focused ultrasound to open the BBB may allow the biomarkers to enter the bloodstream to be detected and measured. If scientists can capture these biomarkers, they may be able to identify the molecular drivers and pathways of Alzheimer’s disease and other diseases caused by neurodegeneration.

According to WUSTL’s press release, this research is, “the first to open the door for noninvasive and targeted diagnosis and monitoring of neurodegenerative disorders with focused ultrasound–mediated liquid biopsy.”

In the study, Dr. Chen’s group first sonicated the cerebral hemisphere to collect general data and compare it with standard blood-based liquid biopsy levels. This method significantly increased two different biomarker levels when compared with conventional methods (p-tau-181–to–mouse tau [m-tau] ratio: 1.7-fold increase, P = .006; p-tau-231–to–m-tau ratio: 1.4-fold increase, P = .048). The team then specifically sonicated the cerebral cortex and hippocampus to collect targeted sonobiopsy data. These spatially targeted applications further increased the biomarker levels by 2.3-fold (P < .001). The application also appeared to be safe, because after the researchers optimized the sonobiopsy parameters, they found no cellular differences in the effect of the ultrasound on the brain when compared with the other side.

“We use the term ‘sonobiopsy’ as a shorthand for focused ultrasound–enhanced blood-based liquid biopsy,” explains Dr. Chen. “Our work has shown that sonobiopsy is a feasible method for releasing Alzheimer’s biomarkers into circulation. If it is translatable to humans, it could help diagnose Alzheimer’s disease and other tau-based neurodegenerative disorders.”

Future questions to answer include learning the qualitative effects of sonobiopsy on plasma biomarker levels, characterizing the effects of each focused ultrasound parameter, determining the optimal blood collection time, and studying whether sonobiopsy can be used to release larger brain-derived protein biomarkers.

“Focused ultrasound provides a unique opportunity to create a window into the brain to study various diseases noninvasively,” said the Foundation’s Director of Clinical Relationships, Suzanne LeBlang, MD. “The ability to increase the quantity and perhaps also the quality of analytes in the peripheral blood may make it possible to detect neurodegenerative disorders such as Alzheimer’s disease earlier, or even differentiate diseases such as a large multiple sclerosis plaque from a brain tumor. The hope is that not only can focused ultrasound–enhanced liquid biopsy aide in the diagnosis of diseases, but, based on the detailed analyses of samples, allow for more precision-based medicine and give each patient the medicine specific for their individual type and stage of disease – almost like antibiotic sensitivity testing.”