Glioblastoma

Focused Ultrasound Therapy

Focused ultrasound is a noninvasive therapy that is transforming the treatment and quality of life for patients with glioblastoma. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.

How it Works
Where the beams converge, the ultrasound produces a variety of therapeutic effects enabling treatment without incisions or radiation. Several different approaches are currently in consideration for glioblastoma, and these will be briefly discussed.

Blood-Brain Barrier (BBB) Disruption
The BBB is normally a protective barrier for the brain, preventing adverse agents that may be in the blood stream from gaining unfettered access to the brain. However, in the setting of glioblastoma, the BBB may still be intact, especially around the peripheral regions of the tumor, and preventing therapeutic agents (like chemotherapy) from accessing this area in sufficient quantities for maximal effect. The temporary disruption of the BBB in the targeted area enables enhanced penetration by the therapeutic agent, and following the treatment, the BBB will re-form, typically in about a day.

Sonodynamic Therapy (SDT)
Certain agents that were originally used as visual dyes to help surgeons differentiate between tumor and normal tissue, have been found to be altered after treatment by focused ultrasound, resulting in materials that are toxic to the tumor in the local area. These agents are also accumulated in tumor cells, which maximizes the detrimental effect on the targeted tissue. Clinical trials are using this technique are to provide targeted therapy to certain tumors, including glioblastomas.

Combination with Radiation
The combination of focused ultrasound and radiation has been shown to enhance the effectiveness of radiation. The joint use of these regimens is being used in patients with recurrent glioblastoma.

Ablation
Thermal ablation is one of the earliest mechanisms of action for focused ultrasound, and it is currently in use for other neurologic indications. While it was in use in some earlier clinical trials for glioblastoma, the recent efforts have shifted to the above mechanisms.

Sono-Sensitive Agents
The use of sound sensitive, ultrasound packages that can carry a variety of therapeutic agents throughout the body, and only release them when they encounter focused ultrasound is a very attractive model for treating a wide variety of diseases, including glioblastoma. This mechanism is being studied in body cancers and preclinical brain lesions currently, and it is likely to be used in clinical trials soon.

Advantages
Current treatments for glioblastoma include surgery, radiation therapy, and chemotherapy, all of which have limitations and side effects.

Focused ultrasound, used alone or in combination with conventional therapies, has the potential for several advantages.

Focused ultrasound is non-invasive, so it does not carry added concerns like surgical wound healing or infection.
Focused ultrasound can reach the desired target without damaging surrounding tissue.
Focused ultrasound does not include the use of ionizing radiation
Focused ultrasound enables enhanced chemotherapy dose for the target, with less impact to the rest of the patient.
It can be repeated, if necessary.

Clinical Trials

The following clinical trials are recruiting patients with brain tumors for focused ultrasound treatment:

Study of Low-Intensity Focused Ultrasound in Combination With Immunotherapy in Newly Diagnosed Unmethylated Glioblastoma (BATs FUS)
This study is using Low Intensity Focused Ultrasound in wild type glioblastoma with T cells armed with bispecific antibodies.

Adjuvant Temozolomide ± 5-Aminolevulinic Acid + Low Intensity Diffuse Ultrasound Sonodynamic Therapy System for Newly Diagnosed Glioblastoma
This study in the US is using low intensity sonodynamic therapy coupled with temozolomide in patients that have newly diagnosed glioblastoma after completion of radiotherapy.

Extracellular Impact of Ultrasound-induced Blood-brain Barrier Disruption
This study of BBBD is looking at the impact of the treatment on other therapeutic and pharmacodynamic substances that may also be in the area when this is accomplished.  

A Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients
This is a study using Avastin for the treatment of recurrent glioblastoma patients in Taiwan.

Safety and Efficacy of Bevacizumab in Combination With NaviFUS System for the Treatment of Recurrent Glioblastoma Multiforme
This clinical trial is organizing and will be done in Virginia.

Evaluate the Safety and Preliminary Efficacy of the Combination of NaviFUS System With Re-irradiation for rGBM Patients
This study is combining the NaviFUS system with re-irratiation in recurrent glioblastoma patients in Taiwan has stopped recruiting.

An Ultrasound-Based Blood Brain Barrier Opening Clinical Trial Using Albumin Bound Paclitaxel to Treat Recurrent Glioblastoma 
This invasive procedure that is similar to focused ultrasound uses an implanted device to treat patients with recurrent glioblastoma.  This project is no longer recruiting patients.

Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With Glioblastoma Brain Tumors 
A clinical trial for patients with glioblastoma for liquid biopsy has completed recruiting patients. 

A multi-site clinical trial is treating patients with recurrent glioblastoma 
This trial is using the Sonocloud-9 implantable device to enhance the treatment with carboplatin has completed recruitment of patients.

The following studies concern focused ultrasound and sonodynamic therapy. 

Sonodynamic therapy with progressive or recurrent glioblastoma
This study is using IV 5 ALA to treat patient with new or progressing glioblastoma at the Mayo Clinic.

A combination of sonodynamic therapy and chemotherapy is being studies in Henan, China.
This study is using Hiporfin® is a brand name for hematoporphyrin derivative, combined with chemotherapy in newly diagnosed glioblastoma in China. This study is recruiting patients by invitation.

Sonodynamic therapy in patients with recurrent glioblastoma.
This study used oral gliolan (5 ALA) which becomes altered in the presence of focused ultrasound and becomes locally toxic to the tumor in Virginia.  

A study of sonodynamic therapy for patient with high grade glioma 
A new clinical trial in the US is using sound activated drugs to treat patients with recurrent high grade glioma, including glioblastoma in Arizona.  

A study of sonodynamic therapy in patients with newly diagnosed glioblastoma 
This study will use low frequency focused ultrasound to activate drugs in patients with newly diagnosed glioblastoma.  This project has been completed.

A study in Germany for patients with newly diagnosed glioblastoma
This study will use oral gliolan (5 ALA) to treat patients prior to surgical resection in Germany. 

The following studies concern tumors in pediatric patients. 

Phase 1/2 Study of Sonodynamic therapy to treat Type 2 Patients with DIPG 
A clinical trial is using sonodynamic therapy to treat pediatric patients who are five years and older with DIPG (diffuse intrinsic pontine glioma).  This project has been suspended.

Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG 
A clinical trial using doxorubicin to treat DIPG has begun in the US. 

Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG 
A clinical trial using doxorubicin to treat DIPG has begun in Canada. 

FUS Etoposide for DMG – A Feasibility Study 
This clinical trial is using focused ultrasound to temporarily open the blood brain barrier to enhance absorption of the chemotherapy agent etoposide.

A Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients (SONOKID)
This clinical trial using the implated Carthera device is recruiting pediatric patients with recurrent malignant brain tumors in multiple locations. 

The Foundation updates these pages regularly, but with the increasing number of clinical trials, we want to be sure that our audience has the latest information available. Therefore, we also added the website search information for the above trials. If you click here, it will take you to the latest information available from https://www.clinicaltrials.gov/.

Find a Treatment Site

Search for a treatment center or clinical trial near you.

Regulatory Approval and Reimbursement

Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for brain tumors, nor is the treatment reimbursed by medical insurance providers.

Preclinical Laboratory Studies

Preclinical studies are underway to investigate the use of various mechanisms of focused ultrasound in the treatment of brain tumors. Examples of these studies include:

Focused ultrasound to temporarily disrupt the BBB and deliver a variety of chemotherapy or immunotherapy drugs, including the dosing and timing (e.g. frequency) of drug administration.
Focused ultrasound to induce an immune response, including a multi-site study investigating the type of immune response elicited by different “modes” of energy delivery.
Focused ultrasound to enable targeted delivery and/or activation of drugs via carrier vehicles (e.g. microbubbles, nanoparticles, liposomes) to enable delivery of high concentrations in the tumor with minimal systemic side effects.
Non-thermal mechanical destruction of tumor using a type of focused ultrasound called histotripsy.

Additional Resources

There are many government bodies and patient groups dedicated to brain tumors, including the following:

Notable Papers

Fiallo Arroyo J, Leon-Rojas JE. The Glymphatic-Immune Axis in Glioblastoma: Mechanistic Insights and Translational Opportunities. Int J Mol Sci. 2026 Jan 16;27(2):928. doi: 10.3390/ijms27020928. PMID: 41596575

Alrashidi M, Ferro F, Almohammadi A, Alyoubi NH, Alsarheed GS, Joseph J, Banerjee S. Efficacy and safety of low- and high-intensity focused ultrasound in glioblastoma: a systematic review of preclinical and clinical studies. Br J Cancer. 2026 Jan 8. doi: 10.1038/s41416-025-03325-6. PMID: 41507561

Lee S, Chang JW. From Ablation to Neuromodulation Platform: The Evolving Role of Magnetic Resonance-Guided Focused Ultrasound in Functional Neurosurgery. J Clin Neurol. 2026 Jan;22(1):17-41. doi: 10.3988/jcn.2025.0563. PMID: 41517810

Jiang Z, Xiao Y, Han M, Hou X, Zhang H, Wang T, Xing W, Li Z. Targeted enhancement of antigen cross-presentation capability of M2-like tumor-associated macrophages to boost glioblastoma immunotherapy. Biomaterials. 2026 May;328:123892. doi: 10.1016/j.biomaterials.2025.123892. Epub 2025 Dec 4. PMID: 41370882

Yan Y, Hwang K, Lee J, Nam KM, Shin S, Yoon B, Zhang Z, Park MH, Kim CY. A novel microbubble delivery platform with high payload of paclitaxel upon focused ultrasound for enhanced glioblastoma treatment. Eur J Pharm Sci. 2025 Dec 12;217:107415. doi: 10.1016/j.ejps.2025.107415. PMID: 41391527

Youngblood MW, Kumari A, Kang YT, Gould A, Habashy K, Gomez M, Lingamarla H, Morey T, Chen L, Congivaram H, Ward R, Zhang H, Sears TK, McCortney K, Pituch KC, Torres Ponce EM, Zarrieneh A, Nieves M, Vandermolen S, Primdahl D, Dixit K, Lukas RV, Kumthekar P, Dmello C, Bouchoux G, Canney M, Amidei C, Stupp R, Nagrath S, Sonabend AM. Dynamic release of extracellular particles after opening of the blood-brain barrier predicts glioblastoma susceptibility to paclitaxel. Nat Commun. 2025 Dec 16;16(1):11045. doi: 10.1038/s41467-025-65681-4. PMID: 41402297

Chang S, Jang T, Lee H, Koo M, Park OK, Choi SH, Yoo RE, Park J. Blood‒brain barrier opening with Golay-coded ultrasound to improve therapeutic consistency in glioblastoma models. Drug Deliv. 2025 Dec 31;32(1):2592940. doi: 10.1080/10717544.2025.2592940. Epub 2025 Dec 3. PMID: 41340188

De Maio A, Lin FH, Stefanovic B, O’Reilly MA. Tissue-type Differences in Focused Ultrasound and Microbubble-mediated Drug Delivery to the Brain Exist at Vessel Level. Theranostics. 2026 Jan 1;16(4):1975-1996. doi: 10.7150/thno.117691. eCollection 2026. PMID: 41356189

Kee H, Lee H, Park J, Jang S, Park S. Integrated focused ultrasound and electromagnetic actuation (FUEM) system for enhanced targeted drug delivery in brain cancer treatment. J Control Release. 2025 Nov 13;389:114408. doi: 10.1016/j.jconrel.2025.114408. PMID: 41241013

Bell MS, Walton CM, Williams MJ, Eckert T, Brown JC, Rowland NC, Sahin O, Strickland BA. Engineering focused ultrasound for glioblastoma. Brain Stimul. 2025 Nov 21;19(1):102986. doi: 10.1016/j.brs.2025.102986. PMID: 41276162

Chen KT, Tsai HC, Huang CY, Liau CT, Ho KC, Toh CH, Chuang CC, Hsu PW, Huang YC, Chang TW, Yeap MC, Chen PY, Lee CC, Lin YJ, Feng LY, Airan RD, Li G, Lim M, Liu HL, Wei KC. Combination of Neuronavigation-Guided Focused Ultrasound and Bevacizumab for Patients With Recurrent Glioblastoma: A Pilot Study. Neurosurgery. 2025 Nov 24. doi: 10.1227/neu.0000000000003851. PMID: 41283685

Sanai N, Tovmasyan A, Tien AC, Chang YW, Margaryan T, Knight W, Hendrickson K, Eschbacher J, Harmon J, Hong A, Yoo W, Furey C, Marcus SL, Alhilali L, Barani I, Mirzadeh Z, Mehta S. An early clinical trial of 5-ALA sonodynamic therapy in recurrent high-grade glioma. Sci Transl Med. 2025 Nov 26;17(826):eads5813. doi: 10.1126/scitranslmed.ads5813. PMID: 41296829

Pouliopoulos AN. Focused ultrasound treatments could increase survival in individuals with glioma. Lancet Oncol. 2025 Dec;26(12):1522-1524. doi: 10.1016/S1470-2045(25)00552-2. PMID: 41308670

Woodworth GF, Anastasiadis P, Ozair A, Chabros J, Bettegowda C, Chen C, Gerstl JVE, Douville C, Mekary RA, Smith TR, Meng Y, Hawkins C, Pople CB, Abrahao A, Llinas M, Heyn C, Bunevicius A, Rezai AR, Ball AJS, Henry K, Sahgal A, Torio E, Ren H, Ahmad H, Arora H, Eisenberg H, Perry J, Carpenter JS, Hynynen K, Pham LC, Anketell MB, Lim-Fat MJ, Xu Z, Cifarelli CP, Sheehan JP, McDannold NJ, Gandhi D, Golby AJ, Lipsman N. Microbubble-enhanced transcranial focused ultrasound with temozolomide for patients with high-grade glioma (BT008NA): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2025 Dec;26(12):1651-1664. doi: 10.1016/S1470-2045(25)00492-9. PMID: 41308679

Wang N, Qing Q, Xue Y, Cai S, Zheng M, Zhang D, Ismail M. Enhancing lipid nanoparticles-mediated RNA delivery to glioblastoma via targeted strategies. J Control Release. 2025 Nov 27:114472. doi: 10.1016/j.jconrel.2025.114472. PMID: 41317918

Chen KT, Tsai HC, Huang CY, Liau CT, Ho KC, Toh CH, Chuang CC, Hsu PW, Huang YC, Chang TW, Yeap MC, Chen PY, Lee CC, Lin YJ, Feng LY, Airan RD, Li G, Lim M, Liu HL, Wei KC. Combination of Neuronavigation-Guided Focused Ultrasound and Bevacizumab for Patients With Recurrent Glioblastoma: A Pilot Study. 

Neurosurgery. 2025 Nov 24. doi: 10.1227/neu.0000000000003851. Online ahead of print.PMID: 41283685

Wang Y, Wen Q, Hu A, Chen X, Liu J, Lin J, Xie Y. Advances in ultrasound-mediated brain drug delivery. J Pharm Pharmacol. 2025 Sep 27:rgaf090. doi: 10.1093/jpp/rgaf090. PMID: 41014313

Hey G, DeYoung C, Dagra A, Gillam W, Lucke-Wold B. An overview of focused ultrasound as a treatment option for gliomas. Expert Rev Neurother. 2025 Sep;25(9):1103-1118. doi: 10.1080/14737175.2025.2534615. Epub 2025 Jul 20. PMID: 40685656

Eckert T, Suresh R, Zobaer MS, Rowland NC. Invasive and non-invasive tumor-treating electric field (TTF) therapy: An exciting advance in oncologic neuromodulation. Brain Stimul. 2025;18(5):1357-1366. doi: 10.1016/j.brs.2025.07.018. Epub 2025 Jul 28. PMID: 40738400

Muhammad S, Maridevaru MC, Roy S, Chen D, Zeng W, Sun L, Zhang Y, Guo B. Piezodynamic Therapy: Unleashing Mechanical Energy and Featuristic Next Generation Therapeutic Paradigms for Glioblastoma. ACS Nano. 2025 Sep 23;19(37):33008-33058. doi: 10.1021/acsnano.5c11629. Epub 2025 Sep 15. PMID: 40948474

Martin E, Roberts M, Grigoras IF, Wright O, Nandi T, Rieger SW, Campbell J, den Boer T, Cox BT, Stagg CJ, Treeby BE. Ultrasound system for precise neuromodulation of human deep brain circuits. Nat Commun. 2025 Sep 5;16(1):8024. doi: 10.1038/s41467-025-63020-1. PMID: 40913042  

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