GBM Workshop 2021 – Navigation Guided Focused Ultrasound: Accelerating Treatment of CNS Disease
The Focused Ultrasound Foundation partnered with the Society for Neuro-oncology (SNO) and the AANS/CNS Tumor Section to host a virtual workshop on May 19–20, 2021, to convene critical stakeholders – researchers, clinicians, industry, government, and others – on the topic of focused ultrasound for glioblastomas.
Tim Liu presented the NaviFUS device (also referred to as NAviFUS-001). NaviFUS uses a novel neuronavigation technique to help simulate the optimal opening of the BBB near a tumor. The neuronavigator uses optical tracking to visualize the position of a surgical instrument by recognizing fiducial markers (registration), which are custom NaviFUS markers.
The standard treatment workflow includes pre-treatment MR imaging to confirm the tumor and select target location, CT scan, personalized treatment plan, and skull penetration estimation that is integrated into the neuronavigator. The procedure takes 30 minutes and consists of 4 steps:
1. setting up the neuronavigation guidance,
2. IV microbubble injection,
3. FUS sonication, and
4. post-treatment MR imaging.
Three NaviFUS hardware technologies were highlighted: focused point steering, passive cavitation detection (PCD) feedback control, and passive imaging of FUS energy. NaviFUS is a phased array with a 256-element transducer, up to 32 elements can be used as a receiver for different functions.
NaviFUS transducer design confers several advantages to the procedure: each element can control output energy and relative phase difference among elements independently, precise control of the focusing point resulting in improved and more efficient dynamic scanning effect, and multiple focal points can be targeted for distribution of ultrasound energy allowing increased flexibility of therapy. The system has a frequency of 500 KHz, burst length of 300 μsec, and an output acoustic pressure of 0.1 to 3 MPa. A single focal beam can have a focus distance of 140 mmm, a focal beam dimension of 3 x 3 x 20 mm, a focal scanning matrix of 43 beams, separated by 3 mm between each other, so that an overall 20 mm a focal beam steering video can be built.
PCD control has been used to validate safe levels of exposure in animals and was shown to reliably open the BBB and minimize the risk of side effects. PCD control is currently being utilized in a first-in-human clinical trial using FUS with bevacizumab. The system also uses transcranial passive imaging to visualize FUS energy. It utilizes 32-channel receiving to construct passive imaging of US energy, a technical breakthrough compared with previous technologies with 4 receiving channels, unable to reconstruct the passive image. This feature allows transcranial mapping of the FUS focal beam target position, resulting in significantly higher signal-to-noise ratio and improved visualization of acoustic emissions.
The software enables users to customize treatment in two- and three- dimension views and estimate transcranial penetration rates. The NaviFUS PCD function can provide personalized acoustic output. The effectiveness of the device and safety parameters were based on extensive translational studies from animal studies. NaviFUS is being tested in clinical trials in brain tumors (BBBO), epilepsy (neuromodulation), and Alzheimer’s disease. NaviFUS first-in-human clinical trial in rGBM demonstrated safety in human use, and BBBO was noted immediately and returned to baseline with 24 hours. Another trial in epilepsy completed in 2020 (n=6) showed decreased EEG power in 2 patients after sonication, and decreased seizure frequency in another 2 patients at 1 to 3 days from baseline.
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