Deep brain ultrasound therapy
Deep brain ultrasound (DBUS) therapy is a form of precision medicine using a technique based on the principle of high-intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS).
The method combines two main components 1:
- guidance component
- MRI of the the head fixed into a stereotactic frame
- use of a coordinates system to plan the ultrasound sonications by controlling the location and extent of thermal tissue destruction
- MRI provides a unique ability to non-invasively map temperature
- therapeutic component
- high power US is focused to a very small point creating particle vibrations which generate heat and subsequent cell death
- temperatures above 56°C for 1 second result in irreversible cell death
- for US ablation applications, the temperature ranges from 65°C to 100°C with minimal heating of adjacent tissues 2
The patient is awake throughout the procedure. A stereotactic frame (similar to that used in deep brain stimulation [DBS]) is fixed onto the head. With the patient lying supine, the frame then fits into a transducer which serves for transcranial focus of US waves. The transducer contains more than a thousand individually electronically controlled US elements. Between the scalp and the hemispheric transducer helmet lies a membrane of cooling water to dissipate heat and minimise the risk of burns.
The term ‘transcranial MR guided focused US' (MRgFUS) has been used to refer to the system with all elements combined.
DBUS has current and future potential for clinical applications:
- essential tremor 3,4 (approved by Food and Drug Administration [FDA] in July 2016)
- Parkinson’s disease and dyskinesia 5 (ongoing clinical trials)
- depression 6 (ongoing clinical trials)
- obsessive compulsive disorder (OCD) 7 (ongoing clinical trials)
- chronic neuropathic pain 8 (ongoing clinical trials)
- brain tumours 9,10 (ongoing clinical trials)
- reversible opening of the blood-brain-barrier to improve delivery of drugs, gene therapy and even stem cells into target areas within the brain 11-14 (pre-clinical research)
The technique contrasts to surgical DBS which is an invasive procedure requiring incisions in the scalp, burr holes and insertion of electrodes into the brain. DBS is currently still undergoing a lot of research and trials to identify new brain targets for different pathologies. Past and current research in DBS will surely lend help to the application of DBUS, with the latter potentially gaining more prominence due to its non-invasive and lower risk profile 2.
HIFU is also being used and trialled for treatment of extracranial pathology such as uterine fibroids (approved by FDA), breast cancer (cleared for use in multiple countries but not yet approved in the US), and prostate cancer (cleared for use in multiple countries including US).15-21 The Focused Ultrasound Foundation (FUSF) serves to accelerate the development and adoption of focused ultrasound - http://www.fusfoundation.org/ 22.
- 1. Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean journal of radiology. 9 (4): 291-302. doi:10.3348/kjr.2008.9.4.291 - Pubmed
- 2. Halpern EJ. Science to Practice: High-intensity focused ultrasound ablation: will image-guided therapy replace conventional surgery?. Radiology. 235 (2): 345-6. doi:10.1148/radiol.2352041774 - Pubmed
- 3. Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W, Schwartz M, Hynynen K, Lozano AM, Shah BB, Huss D, Dallapiazza RF, Gwinn R, Witt J, Ro S, Eisenberg HM, Fishman PS, Gandhi D, Halpern CH, Chuang R, Butts Pauly K, Tierney TS, Hayes MT, Cosgrove GR, Yamaguchi T, Abe K, Taira T, Chang JW. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. The New England journal of medicine. 375 (8): 730-9. doi:10.1056/NEJMoa1600159 - Pubmed
- 4. Bond AE, Dallapiazza R, Huss D, Warren AL, Sperling S, Gwinn R, Shah BB, Elias WJ. A Randomized, Sham-Controlled Trial of Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Trial for the Treatment of Tremor-Dominant, Idiopathic Parkinson Disease. Neurosurgery. 63 Suppl 1: 154. doi:10.1227/01.neu.0000489702.18785.5f - Pubmed
- 5. Schlesinger I, Schlesinger EA, Schlesinger SA, Schlesinger EI, Schlesinger NM, Schlesinger GD, Schlesinger ZM. MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson’s Disease. Parkinson’s Disease. doi:10.1155/2015/219149
- 6. Tsai SJ. (2015). Transcranial focused ultrasound as a possible treatment for major depression. Med Hypotheses, 84; 381-383.
- 7. Jung HH, Kim SJ, Roh D et-al. (2015). Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry, 20; 1205-1211.
- 8. Jeanmonod D, Werner B, Morel A et-al. (2012). Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg, 32; E1.
- 9. Coluccia D, Fandino J, Schwyzer L et-al. (2014). First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. J Ther Ultrasound, 2; 17.
- 10. McDonnold N, Clement GT, Black P et-al. (2010). Transcranial magnetic resonance imaging-guided focused ultrasound of brain tumors: initial findings in 3 patients. Neurosurg, 66; 323-332.
- 11. Fan CH, Ting CY, Lin CY et-al. (2016). Noninvasive, targeted, and non-viral ultrasound-mediated GDNF-Plasmid delivery for treatment of Parkinson’s disease. Sci Rep, 6; 19579.
- 12. Hinow P, Radunskaya A, Mackay SM et-al. (2015). Signaled drug delivery and transport across the blood-brain barrier. J Liposome Res, 26; 233-245.
- 13. Timbie KF, Mead BP and Price RJ. (2015). Drug and gene delivery across the blood-brain barrier with focused ultrasound. J Control Release, 219; 61-75.
- 14. Park J, Zhang Y, Vykhodtseva N et-al. (2012). Targeted and reverible blood-retinal barrier disruption via focused ultrasound and microbubbles. PLoS One, 7; e42754.
- 15. Mahmoud MZ, Alkhorayef M, Alzimami KS et-al. (2014). High-intensity focused ultrasound (HIFU) in uterine fibroid treatment: review study. Pol J Radiol, 79; 384-390.
- 16. Merckel LG, Bartels LW, Köhler MO et-al.(2013). MR-guided high-intensity focused ultrasound ablation of breast cancer with dedicated breast platform. Cardiovasc Intervent Radiol, 36; 292-301.
- 17. Firisawa H, Namba K, Nakahara H et-al. (2007). The evolving non-surgical ablation of breast cancer: MR guided focused ultrasound (MRgFUS). Breast Cancer, 14; 55-58.
- 18. Wu F, Wang ZB, Cao YD et-al. (2007). “Wide local ablation” of localized breast cancer using high intensity focused ultrasound. J Surg Oncol, 96; 130-136.
- 19. Uchilda T, Tomonaga T, Kim H et-al. (2015). Imprived outcomes owing to high-intensity focused ultrasound devices version-up for the treatment of patients with localized prostate cancer. J Urol, 193; 103-110.
- 20. Crouzet S, Chapelon JY, Rouvière O et-al. (2014). Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients. Eur Urol, 65; 907-914.
- 21. Crouzet S(1), Rebillard X, Chevallier D et-al. (2010). Multicentric oncologic outcomes of high-intensity focused ultrasound for localized prostate cancer in 803 patients. Eur Urol, 58; 559-566.
- 22. Focused Ultrasound Foundation website. Accessible from http://www.fusfoundation.org/.