This condition is also known as Diffuse Midline Glioma (DMG)
Focused Ultrasound Therapy
Focused ultrasound is a noninvasive therapeutic technology that is transforming the treatment and quality of life for patients with Diffuse Midline Glioma (DMG), which is the newer name for Diffuse Intrinsic Pontine Glioma (DIPG), a term which is still commonly used. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets in the brain without damaging surrounding normal tissue, and it is currently in clinical trials for patients with DIPG/DMG.
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 this disease, 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 present in the blood stream gaining unfettered access to the brain. However, in the setting of DIPG/DMG, the BBB may still be intact, and can prevent 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, including DIPG/DMG, which maximizes the detrimental effect on the targeted tissue. Clinical trials using this technique are providing targeted therapy to certain tumors, including DIPG/DMG.
Combination with Radiation
The combination of focused ultrasound with radiation has been shown to enhance the effectiveness of radiation. The coupling of these is being used in clinical trials for recurrent glioblastoma, and this may be an area for DIPG/DMG in the future.
Benefits
There is no cure for DIPG, and treatment is limited by the location of these tumors in a very small and eloquent region of the brain called the brainstem. The current standard of care for these tumors is radiation therapy and trials of chemotherapy. These treatments have limited efficacy and are associated with significant side effects. Focused ultrasound has the potential to offer an alternative or complement to the above therapies.
Advantages:
- Noninvasive – no incisions, no risk of infection or bleeding, less pain, and rapid recovery
- Image-guided – precision targeting with minimal damage to surrounding tissue
- Safe, temporary, and repetitive opening of the blood-brain barrier (BBB) – enhancing the delivery of therapeutics directly to the brain target site
- No ionizing radiation – fewer side effects and can be safely repeated
Regulatory Authorizations
Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for DIPG/DMG, nor is the treatment reimbursed by medical insurance providers.
Clinical Trials
The following clinical trials are recruiting patients with DIPG/DMG for focused ultrasound treatment:
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.
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).
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.
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/.
Preclinical Laboratory Studies
- *Sonobiopsy for noninvasive diagnosis of diffuse intrinsic pontine glioma (DIPG) (Washington University in St. Louis, United States)
- *Focused Ultrasound (FUS) promotes blood-brain barrier opening and delivery of GB13 to pediatric high-grade gliomas (University of Colorado Hospital, Anschutz Medical Campus)
- Focused Ultrasound Enhanced Drug Delivery and Sonodynamic Therapy for the Treatment of Diffuse Intrinsic Pontine Glioma (Children’s National Medical Center)
- Focused Ultrasound consortium for treatment of children diagnosed with diffuse midline gliomas (Columbia University, Children’s National Medical Center)
*The Focused Ultrasound foundation is partially or fully funding these studies.
Manufacturers
- INSIGHTEC LTD | Tirat Carmel, Israel | www.insightec.com
- Delsona Therapeutics, Inc. | New York, NY
Additional Resources
There are many government bodies and patient groups dedicated specifically to DIPG/DMG and also for brain tumors in general. Some examples are included below.
DIPG/DMS specific
Brain Tumor
- Medline Plus: A service of the U.S. National Library of Medicine and NIH
- National Cancer Institute’s Brain Tumor Page
- American Brain Tumor Association
- National Brain Tumor Society
- Brain Tumor Research
Media
Clinical trial delivers chemotherapy to pediatric brain tumors using MRI-guided focused ultrasound
U of T News – January 23, 2023
Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient
Children’s National Research Institute – September 19, 2022
SonALAsense Forges Ahead with First Patient Dosing for Devastating Childhood Brain Cancer
SonALAsense – September 13, 2022
Notable Papers
Wu CC, Szalontay L, Pouliopoulos AN, Bae S, Berg X, Wei HJ, Webster Carrion A, Kokossis D, Sethi C, Fino J, Shatravka H, Lipina J, Ji R, Liu K, Yousefian O, Gallitto M, Yoh N, Englander Z, McQuillan N, Tazhibi M, De Los Santos G, Canoll P, Jin Z, Garvin J, Gartrell RD, Pavisic J, Maddocks A, Lignelli A, Feldstein N, Konofagou EE, Zacharoulis S. Blood-brain barrier opening with neuronavigation-guided focused ultrasound in pediatric patients with diffuse midline glioma. Sci Transl Med. 2025 Nov 12;17(824):eadq6645. doi: 10.1126/scitranslmed.adq6645. PMID: 41223245
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
Arrieta VA, Gould A, Kim KS, Habashy KJ, Dmello C, Vázquez-Cervantes GI, Palacín-Aliana I, McManus G, Amidei C, Gomez C, Dhiantravan S, Chen L, Zhang DY, Saganty R, Cholak ME, Pandey S, McCord M, McCortney K, Castro B, Ward R, Muzzio M, Bouchoux G, Desseaux C, Canney M, Carpentier A, Zhang B, Miska JM, Lesniak MS, Horbinski CM, Lukas RV, Stupp R, Lee-Chang C, Sonabend AM. Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas. Nat Commun. 2024 Jun 6;15(1):4698. doi: 10.1038/s41467-024-48326-w. PMID: 38844770
Young CC, Narsinh KH, Chen SR, Ansari SA, Hetts SW, Lang FF, Wintermark M, Kan PT. State of Practice: A Report from the Inaugural SNIS Neurointerventional Oncology Summit. AJNR Am J Neuroradiol. 2025 Jul 1:ajnr.A8902. doi: 10.3174/ajnr.A8902. PMID: 40592540
McVeigh L, Patel T, Miclea M, Schwark K, Ajaero D, Momen F, Clausen M, Adam T, Aittaleb R, Wadden J, Lau B, Franson AT, Koschmann C, Marupudi NI. Updates in Diagnostic Techniques and Experimental Therapies for Diffuse Intrinsic Pontine Glioma. Cancers (Basel). 2025 Mar 10;17(6):931. doi: 10.3390/cancers17060931. PMID: 40149267
Gallitto M, Zhang X, De Los Santos G, Wei HJ, Fernández EC, Duan S, Sedor G, Yoh N, Kokosi D, Angel JC, Wang YF, White E, Kinslow CJ, Berg X, Tomassoni L, Zandkarimi F, Chio IIC, Canoll PD, Bruce JN, Feldstein NA, Gartrell RD, Cheng S, Garvin JH, Zacharoulis S, Wechsler-Reya RJ, Pavisic J, Califano A, Zhang Z, Wu CC. Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma. Neuro Oncol. 2024 Oct 12:noae215. doi: 10.1093/neuonc/noae215. PMID: 39394920
Keating GF, Chesney KM, Patel N, Kilburn L, Fonseca A, Packer RJ, Challa C, O’Brien PF, Donoho DA, Myseros JS, Oluigbo C, Keating RF, Syed HR. MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children’s National Hospital. Neurosurg Focus. 2024 Sep 1;57(3):E6. doi: 10.3171/2024.6.FOCUS24332. PMID: 39217632
Lin C, Smith C, Rutka J. Current immunotherapeutic approaches to diffuse intrinsic pontine glioma. Front Genet. 2024 May 7;15:1349612. doi: 10.3389/fgene.2024.1349612. eCollection 2024. PMID: 38774284
Arms LM, Duchatel RJ, Jackson ER, Sobrinho PG, Dun MD, Hua S. Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma. J Control Release. 2024 May 20;370:835-865. doi: 10.1016/j.jconrel.2024.05.018. PMID: 38744345
Chesney KM, Keating GF, Patel N, Kilburn L, Fonseca A, Wu CC, Nazarian J, Packer RJ, Donoho DA, Oluigbo C, Myseros JS, Keating RF, Syed HR. The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies. Childs Nerv Syst. 2024 May 3. doi: 10.1007/s00381-024-06413-9. PMID: 38702518
‘t Hart E, Bianco J, Bruin MAC, Derieppe M, Besse HC, Berkhout K, Chin Joe Kie LA, Su Y, Hoving EW, Huitema ADR, Ries MG, van Vuurden DG. Radiosensitisation by olaparib through focused ultrasound delivery in a diffuse midline glioma model. J Control Release. 2023 Apr 5;357:287-298. doi: 10.1016/j.jconrel.2023.03.058.
Syed HR, Kilburn L, Fonseca A, Nazarian J, Oluigbo C, Myseros JS, Packer RJ, Keating RF. First-in-human sonodynamic therapy with ALA for pediatric diffuse intrinsic pontine glioma: a phase 1/2 study using low-intensity focused ultrasound : Technical communication. J Neurooncol. 2023 Apr 12. doi: 10.1007/s11060-023-04269-8.
Parekh K, LeBlang S, Nazarian J, Mueller S, Zacharoulis S, Hynynen K, Powlovich L. Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. Neoplasia. 2023 Jan 27;37:100876. doi: 10.1016/j.neo.2023.100876. Online ahead of print.
Dalle Ore C, Coleman-Abadi C, Gupta N, Mueller S. Advances and Clinical Trials Update in the Treatment of Diffuse Intrinsic Pontine Gliomas. Pediatr Neurosurg. 2023 Jan 13. doi: 10.1159/000529099.
Power EA, Rechberger JS, Gupta S, Schwartz JD, Daniels DJ, Khatua S. Drug delivery across the blood-brain barrier for the treatment of pediatric brain tumors – An update. Adv Drug Deliv Rev. 2022 Jun;185:114303. doi: 10.1016/j.addr.2022.114303. Epub 2022 Apr 21.
Tierney TS, Alavian KN, Altman N, Bhatia S, Duchowny M, Hyslop A, Jayakar P, Resnick T, Wang S, Miller I, Ragheb J. Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. J Neurosurg. 2022 Jan 14:1-8. doi: 10.3171/2021.10.JNS21416.
Click here for additional references from PubMed.