Brain Tumors

Focused Ultrasound Therapy

Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with brain tumors. 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. These include temporary opening of the blood-brain barrier, designed to improve levels in the brain of therapeutic agents; thermal ablation; activation of sono-sensitive agents at the target; and combining with radiation therapy for a more pronounced effect. There is also a study using focused ultrasound prior to surgery to help mark the boundary of the tumor extension.

There are several listings for specific diseases within the broader brain tumor category, so you may want to go to these headings for a more detailed description.

DIPG/DMG
Diffuse Intrinsic Pontine Glioma (DIPG) is also referred to as Diffuse Midline Glioma (DMG) is also being investigated using several methods of action. Sonodynamic therapy, (where non toxic agents can respond to ultrasound stimulation to become locally toxic to the tumor), blood brain barrier (BBB) disruption (where the temporary disruption of the BBB can enable better penetration of chemotherapy agents) and the combination of focused ultrasound with radiation can help improve the outcomes.

Glioblastoma
There are several mechanisms of action that are being explored for glioblastoma. Thermal ablation (either complete or partial, which may help with the immune response), sonodynamic therapy, (where non toxic agents can respond to ultrasound stimulation to become locally toxic to the tumor), blood brain barrier (BBB) disruption (where the temporary disruption of the BBB can enable better penetration of chemotherapy agents) and the combination of focused ultrasound with radiation can help improve the outcomes.

Neuroblastoma
There are several mechanisms of action that are being pursued for neuroblastoma. Thermal ablation (either complete or partial, which may help with the immune response), and hyperthermia (temperature elevation) can help with the penetration of chemotherapy agents.

Neurofibromatosis
There are three types of Neurofibromatosis, type 1, type 2, and schwannomatosis, and the common symptom is that the benign tumors grow out with the peripheral nerves and cause numerous symptoms, often associated with pain, as a result. There has been some work proposed on these, and we are looking for clinical trials soon.

Metastatic disease
There is the use of blood brain barrier (BBB) disruption (where the temporary disruption of the BBB can enable better penetration of chemotherapy agents) to allow the treatment of cancers that have metastasized to the brain to be treated. See below for a study on lung cancers that have metastasized to the brain.

Advantages
Current treatments for brain tumors 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 several potential 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
Enhanced chemotherapy dose for the target, with less impact to the rest of the patient.
It can be repeated, if necessary.

Clinical Trials

Focused Ultrasound Blood-Brain Barrier Disruption for the Treatment of High-Grade Glioma in Patients Undergoing Standard Chemotherapy
This clinical trial is using focused ultrasound to temporarily opening the blood brain barrier in patients undergoing maintenance chemotherapy in the Stupp Protocol.

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.

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 also completed recruiting patients.

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.

Pilot Study of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency
This trial will capture wildtype glioblastoma with mismatch repair deficiency in Ohio.

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 the drug 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 taking place in Virginia and is now recruiting patients.  

The following studies concern focused ultrasound and sonodynamic therapy.

Adjuvant Temozolomide ± 5-Aminolevulinic Acid + Low Intensity Diffuse Ultrasound Sonodynamic Therapy System for Newly Diagnosed Glioblastoma
This multicenter trial is evaluating the impact of low-intensity focused ultrasound and 5-ALA on patients with newly diagnosed glioblastoma.

Sonodynamic therapy using focused ultrasound in glioblastomas
This clinical trial in the United Kingdom is using 5-ALA to augment the treatment of patients with glioblastomas.

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.

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

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. This project has completed recruitment of patients.

The following studies concern tumors in pediatric patients.

Focused Ultrasound Blood-Brain Barrier Opening in Pontine Diffuse Midline Glioma to Enhance Temozolomide Therapy: Pilot Feasibility Study (FIDES)
A clinical trial in Utrecht, Netherlands, is aiming to enhance temozolomide therapy in patients with DIPG (diffuse intrinsic pontine glioma).

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. 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 completed patient enrollment in the US.

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 Feasibility Safety Study of Benign Centrally Located Intracranial Tumors in Pediatric and Young Adult Subjects
Centrally located intracranial benign tumors that require intervention in pediatric and young adult patients. This study has been completed. A follow-up, multi-center study treating hypothalamic hamartomas using the same CT.gov number has begun recruiting.

A clinical trial by Carthera is recruiting pediatric patients with recurrent malignant brain tumors in France.

The following studies concern treatment of tumors from the body that have metastasized to the brain.

A clinical trial for patients with breast cancer that has metastasized to their brain is enrolling patients in Canada. The team will us focused ultrasound to open the blood-brain barrier to allow therapeutic medications to more effectively reach the tumor in their brain. This study has completed enrollment. A summary of the first four patients has been published.

A multi-site clinical trial for patients with lung cancer that has metastasized to the brain has begun recruiting patients in the US.

The following study concerns a wide variety of brain tumors.

This clinical trial is for a wide variety of brain tumors that are planned to be biopsied. This study has completed patient enrollment.

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/.

See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >

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

Suggested Reading: Focused Ultrasound for Glioblastoma (PDF), June 2021.

Kapoor A, Strohman A, Ni Y, Isaac G, Raymond J, Legon W. Acoustic Coupling for Double-Blind Human Low-Intensity Focused Ultrasound Neuromodulation. Ultrasound Med Biol. 2026 Aug;52(8):1646-1653. doi: 10.1016/j.ultrasmedbio.2026.04.012. Epub 2026 May 11. PMID: 42115110

Bentayebi K, Louati S, Suwan K, Eljaoudi R, Hajitou A. New developments and prospects for drug delivery in medulloblastoma. Mol Ther Oncol. 2026 Mar 25;34(2):201186. doi: 10.1016/j.omton.2026.201186. eCollection 2026 Jun 18. PMID: 42199604

Hsi P, Gerhardson T, Walker JL, Kim E, Spagnola OT, Isenberg B, Quinnert A, Kaplan DL, Tandon V. Focused ultrasound-induced cavitation in a human brain microphysiological system produces injury signaling biomarkers consistent with blast trauma. NPJ Biomed Innov. 2026 Jun 11;3(1):36. doi: 10.1038/s44385-026-00090-w. PMID: 42277372

Moonen CT, Kassell NF. Current state and future of clinical-focused ultrasound devices in neuro-oncology. Neurooncol Adv. 2025 Dec 2;8(Suppl 4):iv2-iv8. doi: 10.1093/noajnl/vdaf116. eCollection 2026 Jun. PMID: 42281801

Ozair A, Moiz B, Anastasiadis P, Gandhi D, Amatya B, McDermott MW, Woodworth GF, Ahluwalia MS. Focused ultrasound for brain metastases. Neurooncol Adv. 2025 Dec 2;8(Suppl 4):iv40-iv59. doi: 10.1093/noajnl/vdaf131. eCollection 2026 Jun. PMID: 42281803

Meng Y, Lipsman N. Focused ultrasound in neuro-oncology: Realizing the promise of a noninvasive future. Neurooncol Adv. 2026 Mar 20;8(Suppl 4):iv1. doi: 10.1093/noajnl/vdaf231. eCollection 2026 Jun. PMID: 42281804

Lin C, Llinas M, Lipsman N, Krumholtz S, Mithani K, Hynynen K, Rutka J. Focused ultrasound in pediatric neuro-oncology: Current applications and future directions. Neurooncol Adv. 2025 Dec 2;8(Suppl 4):iv79-iv89. doi: 10.1093/noajnl/vdaf019. eCollection 2026 Jun. PMID: 42281805

Sherlock T, Thede AT, Sheybani ND. Focused ultrasound for enhancing cell-based immunotherapies in neuro-oncology. Neurooncol Adv. 2026 Apr 10;8(Suppl 4):iv60-iv78. doi: 10.1093/noajnl/vdag080. eCollection 2026 Jun. PMID: 42281807

Sharma D, McNabb E, Geraghty B, Bailey C, Saifuddin M, Yang W, Giles A, Lim C, Albanese P, Stanisz M, Sahgal A, Czarnota GJ. Evaluation of CNS xenograft brain tumour response to MRI-guided focused ultrasound in combination with radiation therapy. Br J Cancer. 2026 Jun 15. doi: 10.1038/s41416-026-03479-x. PMID: 42298002

Ozair A, Moiz B, Anastasiadis P, Gandhi D, Bettegowda C, Mischel PS, Hong J, Ahluwalia MS, Woodworth GF. Applications of transcranial focused ultrasound for primary brain tumors. Neurooncol Adv. 2025 Dec 2;8(Suppl 4):iv20-iv39. doi: 10.1093/noajnl/vdaf156. eCollection 2026 Jun. PMID: 42281808

Qin Z, Wang Z, Gao C, Yong X, Hua Y, Zhou Y, Xie J. Ultrasound-mediated blood-brain barrier opening for targeted neurological drug delivery. Biomater Adv. 2026 Jun;183:214754. doi: 10.1016/j.bioadv.2026.214754. Epub 2026 Feb 3. PMID: 41666521

Lin J, Zhang X, Zhou Q, Cao W. Multifactorial regulation of ultrasound-induced cavitation by engineered silica nanoparticles. Ultrason Sonochem. 2026 Mar 14;128:107817. doi: 10.1016/j.ultsonch.2026.107817. PMID: 41855993

Landry TG, Forbes AN, Brown JA. Rapid skull decalcification for improved ultrasound transmission in brain imaging and histotripsy: A proof-of-concept study in rat. Ultrasonics. 2026 Mar;159:107859. doi: 10.1016/j.ultras.2025.107859. Epub 2025 Oct 8. PMID: 41075556

Liu D, Shao X, Silva FM, Sanatkhani S, Lee R, Konofagou EE, Wang DJ, Ferrera VP. Alteration of water exchange rates following focused ultrasound-mediated BBB opening in the dorsal striatum of non-human primates: A diffusion-prepared pCASL study. Neuroimage. 2026 Mar;328:121805. doi: 10.1016/j.neuroimage.2026.121805. Epub 2026 Feb 12. PMID: 41690338

Kofoed RH, Elmer B, Noseworthy K, Ardinger J, Wu K, Wischhof E, Vecchio LM, Mahendran TA, Dibia CL, Koch H, Chou SC, Sivadas S, Bu J, Wu SK, McMahon D, Mikloska K, White M, Ramachandran S, Hynynen K, Mueller C, Aubert I. Focused ultrasound expands intra-CSF AAV delivery to deep brain regions in rats and non-human primates. Mol Ther. 2026 Feb 13:S1525-0016(26)00107-3. doi: 10.1016/j.ymthe.2026.02.021. PMID: 41691370

You L, Dai M, Dong C, Zheng M, Zhang K, Ran H, Liu J, Luo P, Zhang Q, Zeng H, Wei J, Yan S, Yang Y, Wang Z, Wen E. Enhanced Sonodynamic Therapy and Radiotherapy Efficacy: Modified Polyethylene Glycol-Bismuth Trioxide Nanoplatform for Targeted Tumor Treatment. Biomater Res. 2026 Feb 18;30:0325. doi: 10.34133/bmr.0325. eCollection 2026. PMID: 41716205

Noel RL, Kugelman T, Karakatsani ME, Shahriar S, Willner MJ, Jimenez DA, Choi CS, Nimi Y, Ji R, Agalliu D, Konofagou EE. Safe focused ultrasound-mediated blood-brain barrier opening is driven primarily by transient reorganization of tight junctions. Commun Eng. 2026 Feb 21. doi: 10.1038/s44172-026-00597-5. PMID: 41723237

Fletcher SP, Mashburn M, Zhang Y, Chisholm A, Martinez S, Power C, McDannold NJ. Comparing the Delivery of Free and Liposomal Doxorubicin Across the Blood-Brain Barrier Following Microbubble-Mediated Focused Ultrasound. Ultrasound Med Biol. 2026 Feb 25:S0301-5629(26)00028-1. doi: 10.1016/j.ultrasmedbio.2026.01.010. PMID: 41748412

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

Lipsman N, Hynynen K, Chen R, Lozano AM. Transcranial focused ultrasound in the human brain. Neuron. 2026 Jan 28:S0896-6273(25)00888-8. doi: 10.1016/j.neuron.2025.11.015. PMID: 41610842

Chen H, Xu Z, Zhang S. Preclinical studies of histotripsy for intracranial tumors. Front Neurol. 2026 Jan 13;16:1727225. doi: 10.3389/fneur.2025.1727225. eCollection 2025. PMID: 41607846

Jo NC, Chernyak V. Advancing Chronic Lesion Assessment After MRI-guided Focused Ultrasound Using T1/T2-weighted Ratio Maps. Radiology. 2026 Jan;318(1):e253878. doi: 10.1148/radiol.253878. PMID: 41591254

Harb M, Nouraein S, Szablowski JO. Site-specific noninvasive delivery of retrograde viral vectors to the brain. Bioeng Transl Med. 2025 Aug 21;11(1):e70062. doi: 10.1002/btm2.70062. eCollection 2026 Jan. PMID: 41573365

Chalet L, Nsimba F, Zambrano Zegarra M, Bertocchini N, Robert J, Augeul L, Leon C, Pillot B, Crola Da Silva C, Canet-Soulas E, Bidaux G. Renewing the theoretical framework of intensity correlation analysis to evaluate blood-brain barrier permeability with spectral fluorescence microscopy in mice. Comput Biol Med. 2026 Feb 1;202:111460. doi: 10.1016/j.compbiomed.2026.111460. Epub 2026 Jan 10. PMID: 41520473

Huang X, Luo X, Su T, Su K, Peng S, Li H. Manganese-based metal-organic frameworks augment postoperative immunotherapy of high-intensity focused ultrasound. J Colloid Interface Sci. 2026 Jan 6;708:139847. doi: 10.1016/j.jcis.2026.139847. PMID: 41518922

Lee H, Menezes V, Zeng S, Kim C, Baseman CM, Kim JH, Padmanabhan S, Premdas P, Djeddar N, Bryksin A, Pandey N, Anastasiadis P, Kim AJ, MacDonald TJ, Bettegowda C, Woodworth GF, Herrmann FJ, Arvanitis C. Data-Driven Feedback Identifies Focused Ultrasound Exposure Regimens for Improved Nanotheranostic Targeting of the Brain. Adv Sci (Weinh). 2026 Jan 7:e17834. doi: 10.1002/advs.202517834. PMID: 41498583

Satapathy M. High- and Low-Intensity Focused Ultrasound. Radiol Technol. 2026;97(3):199-204. doi: 10.1080/02656736.2025.2606701. PMID: 41490698

Lin JW, Fan CH, Kuo TT, Yeh CK. Combining focused ultrasound and microbubbles for enhancing the migration of mesenchymal stem cells to the brain. J Control Release. 2026 Feb 10;390:114585. doi: 10.1016/j.jconrel.2025.114585. Epub 2025 Dec 31. PMID: 41482205

Nowlin P, Zhang Y, Chrisholm A, Zhang H, Dai J, Owusu-Yaw BS, Young SP, Bali D, Upadhyay J, Todd N. Focused ultrasound delivery of enzyme replacement therapy to the brain of Gaa-/- Pompe disease mice. Mol Genet Metab. 2026 Jan;147(1):109294. doi: 10.1016/j.ymgme.2025.109294. Epub 2025 Nov 20. PMID: 41349290

Finlinson E, Snyder M, Riis T, Kubanek J. System for controlled mechanical therapies of the brain. Ultrasonics. 2026 Apr;160:107896. doi: 10.1016/j.ultras.2025.107896. Epub 2025 Nov 29. PMID: 41338146

Kantor J, Morrison M, Vanderslott S, Pollard AJ, Carlisle RC. Public attitudes towards intranasal and ultrasound mediated vaccine delivery: A cross-sectional study in the United Kingdom and United States. Vaccine. 2026 Jan 1;69:127950. doi: 10.1016/j.vaccine.2025.127950. Epub 2025 Nov 11. PMID: 41223692

Davidson B, Schmidt FA, Bichsel O, Hajiabadi MM, Lozano AM. Transcranial Focused Ultrasound: A Transformative Tool for Intracranial Ablation, Drug Delivery, and Neuromodulation. IEEE Rev Biomed Eng. 2026;19:201-215. doi: 10.1109/RBME.2025.3624970. PMID: 41217925

Liu J, He J, Chen X, Wu D. Manipulation of glymphatic system by focused ultrasound: A promising treatment of neurological diseases. J Cereb Blood Flow Metab. 2026 Jan;46(1):162-164. doi: 10.1177/0271678X251383857. Epub 2025 Oct 22. PMID: 41123223

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

Mei CS, Zong S, Madore B, Cosgrove GR, McDannold NJ. Focus correction in MR thermography for increased targeting precision during focused ultrasound procedures. Magn Reson Med. 2026 Feb;95(2):951-961. doi: 10.1002/mrm.70089. Epub 2025 Sep 24. PMID: 40991818

Huang Y, Hynynen K. Technical Parameters and Feedback Control for Blood-Brain Barrier Permeability Enhancement by Focused Ultrasound. IEEE Rev Biomed Eng. 2025 Dec 2;PP. doi: 10.1109/RBME.2025.3636806. PMID: 41329597

Nabavizadeh A, Narsinh K, Kaufmann TJ, Liu H, Pouliopoulos AN, Prada F, Agarwal V, Ellingson BM, Sanvito F, Everson RG, Meng Y, Gandhi D, Chang SM, Wen PY, Ahluwalia MS, Sul N, Hadley L, Leblang S, Shah BR, Arvanitis CD, Burns TC, Moosa S, Woodworth GF. Focused Ultrasound in Brain Tumors: Mechanisms, Imaging Guidance, and Emerging Clinical Applications. AJNR Am J Neuroradiol. 2025 Dec 5:ajnr.A9126. doi: 10.3174/ajnr.A9126. PMID: 41360502

Di Cosmo L, Costa G, Centini FR, Hammond J, Mariola C, Pellicanò F, Totis F, Tam J, Lozano AM. A systematic review of the current trends and future directions of high-intensity focused ultrasound (HIFU) in neurosurgery. Stereotact Funct Neurosurg. 2025 Dec 11:1-19. doi: 10.1159/000549834. PMID: 41379746

Boffelli L, Fimiani C, Núñez NG, Kienzler JC. Synergy of radiotherapy, focused ultrasound, and immunotherapy in the treatment of brain metastases. J Neurooncol. 2025 Dec 15;176(1):124. doi: 10.1007/s11060-025-05379-1. PMID: 41396538

Fadera S, Boas CAWV, Yue Y, Gu Z, Yuan J, De D, Rogers BE, Nazeri A, Chen H. Focused ultrasound-enhanced nose-to-brain delivery of a therapeutic antibody in a large-animal model. Theranostics. 2026 Jan 1;16(5):2156-2169. doi: 10.7150/thno.124354. eCollection 2026. PMID: 41424850

Click here for additional references from PubMed.

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