Clinical Trials Square

Focused Ultrasound Therapy

Focused ultrasound is an early stage, 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.

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

Focused ultrasound has the potential to provide an alternative to invasive surgery or to replace or augment radiosurgery for treatment of tumors in the brain. Focused ultrasound is noninvasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection, blood clots, and mechanical tissue damage associated with surgery. There is no ionizing radiation and, due to precise targeting, no damage to surrounding healthy tissue.

Focused ultrasound may also be a complement to drug therapy, enabling enhanced delivery of chemotherapy or immunotherapy into the brain via temporary opening of the blood-brain barrier and/or enhanced permeability of the blood-tumor barrier. It may also induce an anti-tumor immune response.

Clinical Trials

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

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.

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.

A study using focused ultrasound and bevacizumide in Taiwan is treating recurrent glioblastoma
This study uses neuronavigation to guide temporary opening of the blood-brain barrier, which is aimed at allowing increased drug penetration to patients with recurrent glioblastoma.

Exablate Blood-Brain Barrier Disruption With Carboplatin for the Treatment of rGBM
A new pair of clinical trials has opened in the United States and Canada that use focused ultrasound to open the blood brain barrier (BBB) prior to carboplatin therapy for patients with recurrent glioblastoma.

Safety and efficacy of opening the BBB with the SonoCloud-9 in patients with Glioblastoma
This clinical trial is opening the BBB in patients with recurrent glioblastoma and is designed to help enhance the penetration of chemotherapy. This study began in France and has extended to include US sites.

Exablate Blood Brain Barrier Disruption (BBBD) for Planned Surgery in Glioblastoma
This clinical trial is a feasibility study that will open blood brain barrier prior to surgery in patients with glioblastoma.

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. Click here for a list of tumors treated in this study.

Non-invasive Focused Ultrasound with Oral Pabinostat in Children with Diffuse Midline Gliomas
This clinical trial is recruiting patents and using FUS to help achieve greater chemotherapy penetration to the targeted regions.

Exablate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy
A clinical trial at Severance Hospital, a part of Yonsei University Health System, in Seoul, Korea, is investigating the use of focused ultrasound to open the blood-brain barrier (BBB) and allow chemotherapeutic agents to more efficiently reach the tumors of patients with glioblastoma.

Exablate Blood-Brain Barrier Disruption for Patients with Glioblastoma Undergoing Standard Chemotherapy
This US clinical trial is investigating the use of focused ultrasound to open the BBB to allow chemotherapeutic agents to more efficiently reach the tumors of patients with glioblastoma.

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 is only open to Canadian citizens.

For a full list of known brain tumor clinical trials, please see here.

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

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 2019.

Raspagliesi L, D'Ammando A, Gionso M, Sheybani ND, Lopes MB, Moore D, Allen S, Gatesman J, Porto E, Timbie K, Franzini A, Di Meco F, Sheehan J, Xu Z, Prada F. Intracranial Sonodynamic Therapy With 5-Aminolevulinic Acid and Sodium Fluorescein: Safety Study in a Porcine Model. Front Oncol. 2021 Jun 21;11:679989. doi: 10.3389/fonc.2021.679989. eCollection 2021.

Campwala Z, Szewczyk B, Maietta T, Trowbridge R, Tarasek M, Bhushan C, Fiveland E, Ghoshal G, Heffter T, Gandomi K, Carvalho PA, Nycz C, Jeannotte E, Staudt M, Nalwalk J, Hellman A, Zhao Z, Burdette EC, Fischer G, Yeo D, Pilitsis JG. Predicting ablation zones with multislice volumetric 2-D magnetic resonance thermal imaging. Int J Hyperthermia. 2021;38(1):907-915. doi: 10.1080/02656736.2021.1936215.

Rudie JD, Weiss DA, Colby JB, Rauschecker AM, Laguna B, Braunstein S, Sugrue LP, Hess CP, Villanueva-Meyer JE. Three-dimensional U-Net Convolutional Neural Network for Detection and Segmentation of Intracranial Metastases. Radiol Artif Intell. 2021 Mar 10;3(3):e200204. doi: 10.1148/ryai.2021200204. eCollection 2021 May.

Schregel K, Baufeld C, Palotai M, Meroni R, Fiorina P, Wuerfel J, Sinkus R, Zhang YZ, McDannold N, White PJ, Guttmann CRG. Targeted Blood Brain Barrier Opening With Focused Ultrasound Induces Focal Macrophage/Microglial Activation in Experimental Autoimmune Encephalomyelitis. Front Neurosci. 2021 May 12;15:665722. doi: 10.3389/fnins.2021.665722. eCollection 2021.

Metwally K, Bastiancich C, Correard F, Novell A, Fernandez S, Guillet B, Larrat B, Mensah S, Estève MA, Da Silva A. Development of a multi-functional preclinical device for the treatment of glioblastoma. Biomed Opt Express. 2021 Mar 23;12(4):2264-2279. doi: 10.1364/BOE.419412. eCollection 2021 Apr 1.

Guo Y, Lee H, Fang Z, Velalopoulou A, Kim J, Thomas MB, Liu J, Abramowitz RG, Kim Y, Coskun AF, Krummel DP, Sengupta S, MacDonald TJ, Arvanitis C. Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles. Sci Adv. 2021 Apr 30;7(18):eabf7390. doi: 10.1126/sciadv.abf7390. Print 2021 Apr.

D'Ammando A, Raspagliesi L, Gionso M, Franzini A, Porto E, Di Meco F, Durando G, Pellegatta S, Prada F. Sonodynamic Therapy for the Treatment of Intracranial Gliomas. J Clin Med. 2021 Mar 6;10(5):1101. doi: 10.3390/jcm10051101.

Englander ZK, Wei HJ, Pouliopoulos AN, Bendau E, Upadhyayula P, Jan CI, Spinazzi EF, Yoh N, Tazhibi M, McQuillan NM, Wang TJC, Bruce JN, Canoll P, Feldstein NA, Zacharoulis S, Konofagou EE, Wu CC. Focused ultrasound mediated blood-brain barrier opening is safe and feasible in a murine pontine glioma model. Sci Rep. 2021 Mar 22;11(1):6521. doi: 10.1038/s41598-021-85180-y.

Meng Y, Pople CB, Suppiah S, Llinas M, Huang Y, Sahgal A, Perry J, Keith J, Davidson B, Hamani C, Amemiya Y, Seth A, Leong H, Heyn CC, Aubert I, Hynynen K, Lipsman N. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol. 2021 Mar 10:noab057. doi: 10.1093/neuonc/noab057.

Chen KT, Chai WY, Lin YJ, Lin CJ, Chen PY, Tsai HC, Huang CY, Kuo JS, Liu HL, Wei KC. Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors. Sci Adv. 2021 Feb 5;7(6):eabd0772. doi: 10.1126/sciadv.abd0772. Print 2021 Feb.

Ye D, Yuan J, Yue Y, Rubin JB, Chen H. Focused Ultrasound-Enhanced Delivery of Intranasally Administered Anti-Programmed Cell Death-Ligand 1 Antibody to an Intracranial Murine Glioma Model. Pharmaceutics. 2021 Feb 1;13(2):190. doi: 10.3390/pharmaceutics13020190.

Sheybani ND, Breza VR, Paul S, McCauley KS, Berr SS, Miller GW, Neumann KD, Price RJ. ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma. J Control Release. 2021 Jan 18;331:19-29. doi: 10.1016/j.jconrel.2021.01.023.

Wu SK, Tsai CL, Hynynen K. Novel Treatment Approaches for Brain Tumour from a Blood-Brain Barrier Perspective. Handb Exp Pharmacol. 2021 Jan 17. doi: 10.1007/164_2020_408.

Yang Q, Zhou Y, Chen J, Huang N, Wang Z, Cheng Y. Gene Therapy for Drug-Resistant Glioblastoma via Lipid-Polymer Hybrid Nanoparticles Combined with Focused Ultrasound. Int J Nanomedicine. 2021 Jan 8;16:185-199. doi: 10.2147/IJN.S286221. eCollection 2021.

Poon C, Pellow C, Hynynen K. Neutrophil recruitment and leukocyte response following focused ultrasound and microbubble mediated blood-brain barrier treatments. Theranostics. 2021 Jan 1;11(4):1655-1671. doi: 10.7150/thno.52710. eCollection 2021.

Karakatsani ME, Pouliopoulos A, Liu M, Jambawalikar SR, Konofagou EE. Contrast-free detection of focused ultrasound-induced blood-brain barrier opening using diffusion tensor imaging. IEEE Trans Biomed Eng. 2020 Dec 25;PP. doi: 10.1109/TBME.2020.3047575.

Wei HJ, Upadhyayula PS, Pouliopoulos AN, Englander ZK, Zhang X, Jan CI, Guo J, Mela A, Zhang Z, Wang TJC, Bruce JN, Canoll PD, Feldstein NA, Zacharoulis S, Konofagou EE, Wu CC. Focused Ultrasound-Mediated Blood-Brain Barrier Opening Increases Delivery and Efficacy of Etoposide for Glioblastoma Treatment. Int J Radiat Oncol Biol Phys. 2020 Dec 17:S0360-3016(20)34665-4. doi: 10.1016/j.ijrobp.2020.12.019.

McMahon D, Lassus A, Gaud E, Jeannot V, Hynynen K. Microbubble formulation influences inflammatory response to focused ultrasound exposure in the brain. Sci Rep. 2020 Dec 9;10(1):21534. doi: 10.1038/s41598-020-78657-9.

Ishida J, Alli S, Bondoc A, Golbourn B, Sabha N, Mikloska K, Krumholtz S, Srikanthan D, Fujita N, Luck A, Maslink C, Smith C, Hynynen K, Rutka J. MRI-guided focused ultrasound enhances drug delivery in experimental diffuse intrinsic pontine glioma. J Control Release. 2020 Nov 11:S0168-3659(20)30659-3. doi: 10.1016/j.jconrel.2020.11.010.

Hoque MM, Abdelazim H, Jenkins-Houk C, Wright D, Patel BM, Chappell JC. The Cerebral Microvasculature: Basic and Clinical Perspectives on Stroke and Glioma. Microcirculation. 2020 Nov 10:e12671. doi: 10.1111/micc.12671.

Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma. Front Oncol. 2020 Sep 10;10:1663. doi: 10.3389/fonc.2020.01663. eCollection 2020.

Haumann R, Videira JC, Kaspers GJL, van Vuurden DG, Hulleman E. Overview of Current Drug Delivery Methods Across the Blood-Brain Barrier for the Treatment of Primary Brain Tumors. CNS Drugs. 2020 Sep 23. doi: 10.1007/s40263-020-00766-w.

Ye D, Luan J, Pang H, Yang Y, Nazeri A, Rubin JB, Chen H. Characterization of focused ultrasound-mediated brainstem delivery of intranasally administered agents. J Control Release. 2020 Aug 29;328:276-285. doi: 10.1016/j.jconrel.2020.08.053.

Latifyan S, de Micheli R, Hottinger AF. Physical approaches to treat glioblastoma. Curr Opin Oncol. 2020 Sep 8. doi: 10.1097/CCO.0000000000000689.

Zhu L, Nazeri A, Pacia CP, Yue Y, Chen H. Focused ultrasound for safe and effective release of brain tumor biomarkers into the peripheral circulation. PLoS One. 2020 Jun 3;15(6):e0234182. doi: 10.1371/journal.pone.0234182. eCollection 2020.

Prada F, Sheybani S, Franzini A, Moore D, Cordeiro D, Sheehan J, Timbie K, Xu Z. Fluorescein mediated sonodynamic therapy in a rat glioma model. Journal of Neuro-Oncology, Received: 11 December 2019 / Accepted: 12 May 2020

Sheehan K, Sheehan D, Sulaiman M, Padilla F, Moore D, Sheehan J, Xu Z. Investigation of the tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors. J Neurooncol. 2020 May 2. doi: 10.1007/s11060-020-03504-w.

Beccaria K, Sabbagh A, de Groot J, Canney M, Carpentier A, Heimberger A. Blood-brain Barrier Opening With Low Intensity Pulsed Ultrasound for Immune Modulation and Immune Therapeutic Delivery to CNS Tumors. J Neurooncol 2020 Feb 28. doi: 10.1007/s11060-020-03425-8.

Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg. 2020 Jan 3:1-9. doi: 10.3171/2019.10.JNS192206.

Daniel Y. Zhang, Crismita Dmello, Li Chen, Victor A. Arrieta, Edgar Gonzalez-Buendia, J. Robert Kane, Lisa P. Magnusson, Aneta Baran, C. David James, Craig Horbinski, Alexandre Carpentier, Carole Desseaux, Michael Canney, Miguel Muzzio, Roger Stupp and Adam M. Sonabend Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations. Clin Cancer Res 2019. DOI: 10.1158/1078-0432.CCR-19-2182 Published January 2020

Click here for additional references from PubMed.

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