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Last updated: 4/27/25
Focused ultrasound (FUS) is an innovative, non-invasive therapeutic platform that uses precisely targeted sound waves to treat tissue deep within the body without incisions, anesthesia, or ionizing radiation. In glioblastoma, one of the most aggressive and lethal brain tumors, FUS is being investigated across several mechanisms, including temporary opening of the blood-brain barrier, activation of sonosensitizers, thermal ablation of tumors, immune system stimulation, and enhancing the delivery of chemotherapy.
As a highly flexible technology, focused ultrasound can be tuned for different effects by adjusting parameters like intensity, frequency, and pulse duration. Research centers such as Sunnybrook Health Sciences Centre (Canada), Brigham and Women's Hospital (USA), University of Maryland, and the Focused Ultrasound Foundation are pioneering clinical trials aimed at bringing this technology to routine glioblastoma care.
The blood-brain barrier (BBB) protects the brain but blocks many therapeutic agents from reaching brain tumors. Focused ultrasound combined with intravenous microbubbles can temporarily and safely disrupt the BBB at targeted sites, enhancing drug penetration.
Mechanism: Microbubbles oscillate under the influence of ultrasound waves, mechanically loosening tight junctions between endothelial cells lining brain capillaries. The opening is transient (lasting hours) and reversible.
Clinical Trials and Devices:
About SonoCloud-9: SonoCloud-9 consists of nine small ultrasound transducers embedded within a single implantable device. It is surgically implanted during a brief procedure and can be activated externally during outpatient visits, without the need for general anesthesia or MRI guidance. It enables frequent BBB opening sessions synchronized with chemotherapy cycles, significantly improving drug access to brain tumors compared to traditional methods.
Advantages: Regular, non-invasive activation; safe repeated BBB openings; does not require hospitalization; compatible with many chemotherapy protocols.
Challenges: Requires minor surgery to implant the device; infection risk needs to be minimized with careful surgical technique and maintenance protocols.
Sonodynamic therapy (SDT) is an emerging, non-invasive technique that combines a sonosensitizing drug with focused ultrasound to selectively destroy cancer cells. This strategy shows promise in treating aggressive brain tumors like glioblastoma.
Mechanism: A sonosensitizer, such as 5-aminolevulinic acid (5-ALA), is administered and accumulates in tumor cells. When activated by low-intensity ultrasound, the sonosensitizer produces reactive oxygen species (ROS) that kill the tumor cells without harming surrounding healthy brain tissue.
Recent Developments: We recently hosted a webinar about sonodynamic therapy, featuring leading experts discussing new research and clinical trial results. You can view the webinar here: VirtualTrials Sonodynamic Therapy Webinar.
Key Companies:
Challenges: Sonodynamic therapy requires precise delivery of both the sonosensitizer and ultrasound activation. Continued innovation is needed to optimize treatment protocols, ensure safety, and validate clinical benefits across larger patient populations.
Focused ultrasound can elevate the temperature of the tumor slightly, sensitizing it to chemotherapy and radiation therapy without causing direct cell death.
Mechanism: Increases tumor perfusion, improves oxygenation, and temporarily enhances blood vessel permeability, boosting therapeutic delivery.
Clinical Trials:
Challenges: Precise control of heating is critical in brain tissue to avoid damage to healthy structures.
High-intensity focused ultrasound (HIFU) can thermally ablate tumor tissues, providing a potential non-invasive alternative to surgery for some glioblastoma patients.
Mechanism: Ultrasound waves converge at a focal point, rapidly raising tissue temperatures above 55 degrees Celsius and causing coagulative necrosis.
Clinical Examples:
Focused ultrasound can enhance the immune system's response against glioblastoma by disrupting tumor barriers and exposing hidden antigens.
Mechanisms:
Clinical Trials:
Challenges: Overcoming the highly immunosuppressive glioblastoma microenvironment remains a significant hurdle.
Focused ultrasound not only opens the BBB but also improves drug distribution through mechanical forces such as cavitation, acoustic streaming, and microstreaming effects.
Examples: Researchers are exploring nanoparticle and liposomal drug carriers that can be better distributed through tumor tissue using FUS-mediated transport enhancement techniques.
Challenges: Finding the optimal ultrasound settings and drug formulations for maximal synergistic effects is still under investigation.
Several promising avenues are being pursued to make focused ultrasound a standard tool in glioblastoma management:
Focused ultrasound represents a transformative technology for glioblastoma, offering new hope for safer, more effective, and more personalized treatments. As research progresses, devices like the SonoCloud-9 and techniques like sonodynamic therapy may significantly improve survival and quality of life for patients facing this devastating disease.
For more information about ongoing clinical trials and new developments, visit the Virtual Trials homepage.