Deep brain ultrasound therapy

Deep brain ultrasound (DBUS) therapy, also known as transcranial MR-guided focused ultrasound (MRgFUS), 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).

Technique

The method combines two main components ¹:

• guidance component

  • MRI of 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 ultrasound is focused to a very small point creating particle vibrations that generate heat and subsequent cell death

  • temperatures above 56°C for 1-second result in irreversible cell death

  • for ultrasound 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 ultrasound waves. The transducer contains more than a thousand individually electronically controlled ultrasound elements. Between the scalp and the hemispheric transducer helmet lies a membrane of cooling water to dissipate heat and minimize the risk of burns.

The technique contrasts with 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.

Indications

DBUS has current and future potential for clinical neuropsychiatric applications:

• essential tremor ^3,4 (FDA and international approval); the primary target is the ventral intermediate nucleus (ViM) within the thalamus

• Parkinson disease ⁵ (FDA and international approval); the thalamus is targeted for tremor, and the globus pallidus or subthalamic nucleus are targeted for dyskinesia 

• depression ⁶ (International approval but not FDA approved)

• obsessive-compulsive disorder (OCD) ⁷ (international approval but not FDA approved)

• chronic neuropathic pain ⁸ (international approval but not FDA approved)

• brain tumors ^9,10 (ongoing clinical trials)

• drug-refractory epilepsy ²² (ongoing clinical trials)

• reversible opening of the blood-brain-barrier to improve the delivery of drugs, gene therapy and even stem cells into target areas within the brain ^11-14 (pre-clinical research)

HIFU is also being used and trialed for the 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 United States of America), and prostate cancer (cleared for use in multiple countries including the United States of America) ^15-21.