Tumors of the Central Nervous System (CNS), which includes the brain and spine, can be benign or malignant (cancerous). Benign CNS tumors are more common, with more than 500,000 people in the U.S. living with a non-cancerous tumor and about 140,000 with a malignant tumor. Most malignant tumors are metastatic, having spread from cancers primarily located in other organs. Malignant brain tumors are inherently serious and life-threatening — they are invasive and destroy brain tissue, as well as create pressure on brain because of the limited space within the skull.
Not all brain tumors cause symptoms. The most common symptoms that occur could be the result of increased intracranial pressure (headache, vomiting), or damage to/irritation of nerve tissue (loss of neurological functions, seizures). Diagnosis is based on clinical evaluation and imaging.
Treatment options for brain tumors include surgical removal or destruction of the tumor using heat, radiotherapy, and chemotherapy, or a combination of two or more of these modalities:
- Surgery: complete or partial resection of the tumor to remove as much as possible.
- Radiotherapy: the most commonly used nonsurgical treatment for brain tumors.
- Chemotherapy: seldom used to treat brain tumors, as the blood-brain barrier prevents the drugs from reaching the cancerous cells.
Focused Ultrasound Treatment
Focused ultrasound has tremendous potential to improve the treatment of certain brain tumors. As this modality is non-invasive and accurate, it may be able to thermally ablate only targeted tissue while sparing healthy adjacent brain tissue. This is especially critical in the brain where any damage to healthy tissue can result in significant loss of function. In addition, focused ultrasound has the potential to reduce the risk for infection and bleeding, lower procedural morbidity by avoiding the need to open the skull, and avoid the toxicity of radiation.
Currently, focused ultrasound can effectively target small tumors located in the center of the brain, in areas such as the medial part of the thalamus. The Foundation is conducting and funding technical research to expand the area of the brain that can be reached and treated by focused ultrasound in collaboration with academia and industry.
For the first time in March 2014, clinicians at the FUS Center of University Children's Hospital Zurich used focused ultrasound to successfully ablate a portion of a recurrent glioma, a procedure that established the feasibility and safety of the treatment. Additional clinical trials to prove safety and efficacy are required to translate this milestone into an available treatment. Read the report.
In addition to the ongoing clinical research to evaluate the use of Focused Ultrasound for thermal ablation of brain tumors, several other Focused Ultrasound brain tumor treatment approaches are being investigated.
Researchers at UVa in collaboration with the Foundation and InSightec are conducting a pre-clinical study to evaluate the safety and efficacy of a low frequency system, (220 kHz), as a tool for noninvasive MR guided trans-cranial thermal ablation of tumors in the brain. The advantages of using a lower frequency compared to the currently active clinical system include the potential to reach much more of the brain and treat larger volume in less time.
Another approach that is being investigated is the use of focused ultrasound to enable the targeted delivery and/or activation of drugs. The goal of this research is to deliver drugs into the brain tumor in high concentrations while minimizing systemic side-effects. A related approach is to use the temporary BBB opening from FUS to allow systemic agents to penetrate and have impact on the tumor.
A third treatment application is non-thermal destruction of tissue with Focused Ultrasound which is being evaluated by several sites. In this method the acoustic energy is used to create non-thermal mechanical effects at the focal point which can damage and destroy tissue. Recently investigators at Brigham and Women’s Hospital were able to create non-thermal brain lesions using focused ultrasound in combination with micro-bubbles.
For a full list of known brain tumor clinical trials, please see here.
The following ongoing studies are recruiting patients with brain tumors for focused ultrasound treatment:
MRI-Guided Focused Ultrasound Feasibility Study for Brain Tumors at Brigham & Women's Hospital and Swedish Medical Center in Seattle
Purpose: Investigating the treatment of recurrent metastatic brain tumors using focused ultrasound
- Brigham & Women's Hospital - Boston, Massachusetts
Contact: Danielle Chamberlain at 617.525.8596 or
- Swedish Medical Center - Seattle, Washington
Contact: Colleen Ottinger at 206.320.3070 or
ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) Treatment of Brain Tumors at Sunnybrook Toronto
Purpose: Investigating a first-line treatment using focused ultrasound for patients with metastatic brain tumors
Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound at Sunnybrook Toronto
Purpose: evaluate the safety of BBB disruption using transcranial MRI-guided focused ultrasound in conjunction with a contrast agent to increase doxorubicin in brain tumours
Regulatory Approval and Reimbursement
Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for brain tumors, nor is it reimbursed by medical insurance providers for such.
More InformationThere are many government bodies and patient groups dedicated to brain tumors, including the following:
- 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
FUS for Glioblastoma Workshop PDF - November 9-10, 2015
Alkins R, Burgess A, Kerbel R, Wels WS, Hynynen K. Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival.
Neuro Oncol. 2016 Jan 26. pii: nov318.
Mead BP, Mastorakos P, Suk JS, Klibanov AL, Hanes J, Price RJ. Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound. J Control Release. 2016 Feb 10;223:109-17. doi: 10.1016/j.jconrel.2015.12.034. Epub 2015 Dec 28.
Ter Haar G. HIFU Tissue Ablation: Concept and Devices. Adv Exp Med Biol. 2016;880:3-20. doi: 10.1007/978-3-319-22536-4_1.
Werner B, Martin E. Transcranial focused ultrasound: Neurological applications of magnetic resonance-guided high-intensity focused ultrasound. Radiologe. 2015 Nov;55(11):976-80, 982-3. doi: 10.1007/s00117-015-0026-1. German.
Timbie KF, Mead BP, Price RJ. Drug and gene delivery across the blood-brain barrier with focused ultrasound. J Control Release. 2015 Dec 10;219:61-75. doi: 10.1016/j.jconrel.2015.08.059. Epub 2015 Sep 8.
Ghanouni P, Pauly KB, Elias WJ, Henderson J, Sheehan J, Monteith S, Wintermark M. Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications. AJR Am J Roentgenol. 2015 Jul;205(1):150-9. doi: 10.2214/AJR.14.13632.
Endo S, Kudo N, Yamaguchi S, Sumiyoshi K, Motegi H, Kobayashi H, Terasaka S, Houkin K. Porphyrin derivatives-mediated sonodynamic therapy for malignant gliomas in vitro. Ultrasound Med Biol. 2015 Sep;41(9):2458-65. doi: 10.1016/j.ultrasmedbio.2015.05.007. Epub 2015 Jun 10.
Kovacs Z, Werner B, Rassi A, Sass JO, Martin-Fiori E, Bernasconi M. Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models. J Control Release. 2014 May 27. pii: S0168-3659(14)00336-8. doi: 10.1016/j.jconrel.2014.05.033.
Monteith S, Sheehan J, Medel R, Wintermark M, Eames M, Snell J, Kassell NF, Elias WJ. Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery. J Neurosurg. 2013 Feb;118(2):215-21. doi: 10.3171/2012.10.JNS12449. Epub 2012 Nov 23
McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS. Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res. 2012 Jul 15;72(14):3652-63
Park J, Zhang Y, Vykhodtseva N, Akula JD, McDannold NJ. Targeted and reversible blood-retinal barrier disruption via focused ultrasound and microbubbles. PLoS One. 2012 Aug 13;7(8):e42754 Epub
McDannold N, Clement GT, Black P, Jolesz F, Hynynen K. Transcranial magnetic resonance imaging- guided focused ultrasound surgery of brain tumors: initial findings in 3 patients. Neurosurgery 66:323-332; discussion 332, 2010
Hynynen K, Clement G. Clinical applications of focused ultrasound-the brain. Int J Hyperthermia 23:193-202, 2007
Ram Z, Cohen ZR, Harnof S, Tal S, Faibel M, Nass D, et al. Magnetic Resonance Imaging-Guided, High-Intensity Focused Ultrasound For Brain Tumor Therapy. Neurosurgery 59:949-956, 2006
Click here for additional references from PubMed.
Video courtesy of InSightec