Your Donations in Action: Arash Nazeri, MD

Sonobiopsy for Opening of the Blood-Brain Barrier for Targeted Therapy

Arash Nazeri MD

A hallmark of tauopathies like Alzheimer’s disease and frontotemporal lobar degeneration is the deposit of pathologic tau protein species in the brain, leading to downstream events that culminate in neuronal death.

Current PET imaging and recently developed plasma biomarkers are highly sensitive tools that allow for early detection of tauopathies. However, there is notable variation in the exact subtypes of tau protein present in the brains of patients with tauopathies that is not adequately captured by these methods.

Sonobiopsy, a focused US (FUS)-mediated, blood-based liquid biopsy, is an emerging technique that allows targeted, reversible, focal opening of the blood-brain barrier (BBB) to release brain-derived biomarkers from the anatomically targeted brain region to the blood. In effect, by comparing plasma biomarker levels before and after BBB opening, sonobiopsy allows temporally controlled noninvasive sampling of the brain tissue environment.

In a proof-of-principle preclinical study, Arash Nazeri, MD, assistant professor at the Mallinckrodt Institute of Radiology, Washington University in St. Louis, and colleagues showed that FUS-induced BBB opening increases circulating levels of pathogenic tau species in a transgenic mouse model of tauopathy.

In a follow up study on the early neurodegenerative stages of the model, they showed that spatially targeted sonobiopsy (targeting either the hippocampus or cerebral cortex) resulted in the release of NfL protein, a secondary biomarker for neurodegeneration.

Together these illustrate that sonobiopsy can increase the diagnostic yield of brain-derived plasma biomarkers and allow spatially selective liquid biopsy.

“By releasing brain-derived pathogenic proteins, sonobiopsy could facilitate development of personalized therapeutic strategies for neurodegenerative disorders,” Dr. Nazeri said.

The RSNA R&E Foundation grant gave Dr. Nazeri the opportunity to co-lead a multidisciplinary research project, mentor students and collaborate with other scientists from various backgrounds.

“This grant allowed me to establish myself in the emerging field of MR-guided focused US research and helped me build the foundation for my future independent work in this area,” Dr. Nazeri said.

For More Information

Access the Radiology study, “Focused Ultrasound-mediated Liquid Biopsy in a Tauopathy Mouse Model.”

Connect with Dr. Nazeri on Twitter.

Learn more about R&E Funding Opportunities.

Read our previous Your Donations in Action article.