Key Points
- Results from the first-in-human pilot trial using the NaviFUS device to open the blood-brain barrier in six patients with recurrent glioblastoma were published in Science Advances.
- Researchers used a device that combines neuronavigation and a manually operated, frameless focused ultrasound system.
The clinical results from Taiwan-based NaviFUS’ first phase I clinical trial to open the blood-brain barrier (BBB) in patients with glioblastoma has been published in the journal Science Advances. In “Neuronavigation-Guided Focused Ultrasound for Transcranial Blood-Brain Barrier Opening and Immunostimulation in Brain Tumors,” researchers enrolled six patients with recurrent glioblastoma who were scheduled to undergo surgical resection.
“This is an important study to show the breadth and depth of worldwide research that is currently underway using focused ultrasound to treat these deadly brain tumors,” said Foundation Chairman Neal F. Kassell, MD. “We congratulate the authors and NaviFUS for developing this novel, safe, and innovative way to use the technology.”
The trial design included escalating doses of focused ultrasound plus 4.8 ml of SonoVue microbubbles to transiently open the BBB at the targeted brain site. The 500-kHz NaviFUS system tested three different energy doses to open the BBB by assigning two patients to each dosing group.
Importantly, it was a first-in-human clinical trial using the NaviFUS device, which combines neuronavigation and a mobile, manually operated focused ultrasound system. It does not require a frame attached to the skull, a large space, or an expensive intraoperative MRI suite. The procedure was efficiently performed within 15 minutes, and the system achieved target accuracy within less than a 3-mm error of deviation.
While successfully establishing the safety and feasibility of the device and its navigation guidance system, the investigators also observed a dose-dependent BBB-opening effect that reverted to baseline within 24 hours after treatment. The BBB-opening effect was confirmed in the targeted regions using contrast-enhanced MRI perfusion. The researchers measured the signal intensity changes on the MR images to compare the capillary permeability at various time points. Surgical resection of the tumor tissue occurred seven days after the sonication. When performing histological assessment of the tumor tissue removed after surgery, the research team found no clinical immunologic response in the study participants.
“Because the NaviFUS system does not require a stereotactic frame, it is more comfortable for patients and requires less management from medical staff,” said NaviFUS CEO, Arthur Lung, PhD. “Furthermore, we have designed it to be compatible with any neuronavigation system, which is something that most hospitals already own and use.”
The published manuscript also reports results from a parallel preclinical study in an orthotopic rat model of human malignant glioma. The rat study was conducted using a higher dose of energy to provide possible evidence of focused ultrasound–induced immune modulation as an additional therapeutic benefit. In this model, immunological changes were analyzed on day 0 and day 7 after focused ultrasound treatment with two different sonication levels. As the focused ultrasound energy increased, the rats exhibited increasing levels of anti-tumorigenic immune cells within the tumor. Further studies will determine whether this effect is achievable in human subjects.