Researchers Define First Technical Framework for Using Focused Ultrasound to Open the Blood-Brain Barrier
A multi-institutional team led by the University of Maryland School of Medicine (UMSOM) and Brigham and Women’s Hospital has published the first comprehensive technical description for reliably opening the blood-brain barrier (BBB) using focused ultrasound. The findings, detailed in Device, provide a foundation for expanding the clinical use of this technique in treating patients with glioblastoma and other neurological conditions.
The study was directed by Graeme Woodworth, MD, Professor and Chair of Neurosurgery at UMSOM and Director of the Brain Tumor Treatment and Research Program at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). His team collected data from 34 glioblastoma patients, who underwent up to six monthly treatment cycles, totaling 972 focused ultrasound sonications. The goal was to establish how ultrasound could be applied most effectively to achieve reliable and repeatable BBB opening.
Researchers found that acoustic emissions signals—the echoes generated by circulating microbubbles activated by ultrasound energy—served as a predictive marker for when the blood-brain barrier was successfully opened. These measurements, they noted, offer a pathway to monitor, compare, and eventually standardize treatment protocols across patients, devices, and institutions.
“Given the expanding availability of multiple ultrasonic energy delivery devices, varying treatment parameters, and differing real-time monitoring and control approaches, a significant, unmet need exists for defining and standardizing blood-brain barrier opening treatments with focused ultrasound,” Dr. Woodworth said. “Acoustic emissions monitoring and acoustic emissions-derived dosing regimens offer an opportunity for a unifying concept in focused ultrasound. The data and analysis provided in this study serve to advance this methodological paradigm and the focused ultrasound field.”
The blood-brain barrier functions as a protective security system, shielding the brain from toxins and microbes but also blocking many therapeutic agents, including chemotherapy. Focused ultrasound aims to temporarily open this barrier. In the procedure, microscopic gas-filled bubbles are injected into the bloodstream and activated by low-intensity ultrasound waves targeted to specific brain regions. MRI monitoring confirms when the BBB has been safely and effectively disrupted.
“Upon excitation under low-intensity ultrasound waves, the microbubbles oscillate within the energy field, causing temporary mechanical perturbations in the walls of the brain blood vessels,” explained Pavlos Anastasiadis, PhD, Assistant Professor of Neurosurgery at UMSOM.
The research builds on early work from the 1990s, when scientists at Brigham and Women’s first demonstrated that microbubbles could open the BBB. “Our work builds upon these discoveries, finding a safe and feasible technique that allows us to repeatedly open the blood-brain barrier in patients with glioblastoma prior to chemotherapy,” said Alexandra J. Golby, MD, senior author and Director of Image-Guided Neurosurgery at Brigham and Women’s.
The data came from a subset of glioblastoma patients enrolled in a clinical trial led by Dr. Woodworth, in which focused ultrasound was used alongside standard chemotherapy. Results from this trial are expected to be published soon.
Taofeek K. Owonikoko, MD, PhD, Executive Director of UMGCCC, praised the achievement: “This work provides the first detailed technical descriptions of acoustic emissions dosing in targeted focused ultrasound and will inform clinical and regulatory advancement of this treatment.”
Currently, a larger pivotal trial called LIBERATE (NCT05383872) is underway, co-led by Dr. Woodworth in collaboration with ReFOCUSED, a North American research consortium of more than 20 sites dedicated to advancing MRI-guided focused ultrasound for drug delivery and diagnostics.
The study was supported by Insightec Inc., the device’s manufacturer, and the Focused Ultrasound Foundation.