UM conducting first U.S. clinical trial of focused ultrasound to open blood-brain barrier

The University of Maryland School of Medicine in Baltimore announced that it is launching a clinical trial to use magnetic resonance-guided focused ultrasound (MRgFUS) to open the blood-brain barrier (BBB) in up to 15 patients with suspected glioblastoma undergoing brain surgery at the University of Maryland Medical Center to remove suspicious tumors. The U.S. Food and Drug Administration (FDA) approved the clinical trial, the first of its kind in the United States, in October 2017.

On the morning of the surgery, patients will undergo a standard magnetic resonance imaging (MRI) exam as part of the preoperative planning process.  Guided by the MRI, ultrasound will target a precise region within the tumor as injected microbubbles are circulating within the bloodstream. The microbubbles will oscillate within the ultrasound field, causing temporary openings in the walls of the brain blood vessels, and allowing the MRI contrast agent to pass into the brain tissue. The MRI scan will then be completed, documenting the extent to which the blood-brain barrier was disrupted.

The data from the MRI will be used by an intraoperative stereotactic neuro-navigation system to localizes the tumor within the brain. After the surgery, researchers will also rigorously examine the tissue that was removed to study the potential therapeutic and other effects from the focused ultrasound procedure.

In this initial trial, the increased amount of contrast enhancement within the tumor provided by the focused ultrasound procedure may help the 3D navigation during the surgery, according to principal investigator Graeme F Woodworth, MD, professor of neurosurgery and director of the Brain Tumor Treatment and Research Center at the university’s Stewart Greenebaum Comprehensive Cancer Center.

The trial is a safety and feasibility study. “If successful, this approach would allow us to use chemotherapy and other therapies in the brain in ways that are currently not possible,” he said, “Ninety-eight percent of currently approved drugs don’t enter the brain because of the blood-brain barrier. If we can selectively open the BBB, in the future we could give a much lower dose of powerful drugs, which would likely reduce toxic side effects and make treatments safer and more effective for patients.”

The University of Maryland also announced that a second FDA-approved clinical trial will be opened to patients later this year. For this clinical trial, newly diagnosed glioblastoma patients will undergo BBB opening prior to treatment with standard chemotherapy, temozolomide. MRgFUS will be used with microbubbles to target the areas where tumor recurrence is most likely to occur.