Key Points
- A multisite team from Italy used a custom ultrasound system to simultaneously open the blood-brain barrier and monitor real-time microbubble distribution.
- This research was partially funded by the Foundation, and four of the authors are former global interns.
Ultrasound Guided Blood Brain Barrier Opening using a Diagnostic Probe in a Whole Brain Model

Researchers have demonstrated a novel method for temporarily opening the blood-brain barrier (BBB) using a diagnostic ultrasound probe. This preclinical study, led by Francesco Prada, MD, at Istituto Neurologico Carlo Besta in Milan, Italy, along with colleagues at the University of Florence, used a custom ultrasound system (ULA-OP – University of Florence) to simultaneously deliver low-intensity pulsed ultrasound for BBB opening and monitor real-time microbubble distribution. The ULA-OP’s dual-mode technique enables direct feedback during sonication, improving accuracy while reducing the risk of off-target effects.
To determine the most effective approach, the researchers tested several ultrasound settings and found dedicated patterns successful in temporarily opening the BBB. They then added real-time imaging, creating a new version that allowed them to track how microbubbles moved and responded during treatment. The flexibility of the ULA-OP system was essential in enabling this dual function—allowing seamless switching between treatment and imaging modes without hardware modifications. The ability to treat and visualize the brain at the same time could be especially useful in operating rooms or in future procedures involving implantable ultrasound-friendly windows in the skull.
“The findings from this study represent a major step toward more precise, image-guided drug delivery to the brain,” said Dr. Prada.
“Using ULA-OP for the first time in therapeutic applications was both a challenge and an inspiration for future developments,” commented Dr. Francesco Guidi, PhD, an engineer at the University of Florence.
This research was partially funded by the Focused Ultrasound Foundation and contributes to a broader initiative of integrated, real-time neurointerventions. Four of the authors—including first authors Matteo Gionso and Erica Herlin—are former Foundation global interns.
“This research demonstrates the Foundation’s pivotal role, not only in funding innovative focused ultrasound research, but also in supporting early-career scientists as they contribute to research with real potential to change how we diagnose and treat a wide range of serious medical conditions,” said Dr. Prada.