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  • Updated 12.05.2021
  • Released 12.05.2021
  • Expires For CME 12.05.2024

Use of focused ultrasound in neurologic disorders

Introduction

Overview

Focused ultrasound is a noninvasive neuromodulation technique used to affect the structure and function in the living brain and peripheral nervous system. Unlike diagnostic ultrasound, it can be focused to a burning point by an acoustic lens. High-intensity focused ultrasound uses nonionizing ultrasonic waves to precisely heat or ablate tissue, such as tumors, via thermal and mechanical mechanisms.

Use of magnetic resonance-guided focused ultrasound (MRgFUS) was first cited and patented in 1992. The InsighTec ExAblate 2000 was the first MRgFUS system to obtain FDA market approval in the United States. The technology was later transferred to InsighTec in Haifa Israel in 1998 and then to the United States. In 2016, the United States FDA approved the first focused ultrasound device to treat essential tremor in patients who have not responded to medication. Exablate Neuro used magnetic resonance images taken during the procedure to guide the delivery of focused ultrasound to destroy brain tissue in a tiny area responsible for causing tremors.

Key points

• Focused ultrasound is a noninvasive neuromodulation technique used to affect the structure and function of the living nervous system.

• Focused ultrasound can heat or ablate tissue, such as tumors, via thermal and mechanical mechanisms.

• Microbubble-mediated, focused ultrasound-induced opening of the blood-brain barrier can be used for targeted drug delivery to the brain.

• Future applications of focused ultrasound therapy potentially have a favorable competitive role against established technologies, including deep-brain stimulation and stereotactic radiosurgery, particularly regarding tissue ablation, blood-brain-barrier opening, and gene therapy.

Historical note and terminology

Ultrasound is defined as mechanical waves with frequency higher than human audible sound (conventionally 20,000 Hz) that can travel through all types of matter: gases, liquids, solids, and plasma. Subsequently, the mechanical waves can be reflected, refracted, or attenuated by the medium. Although discovered in 1880, the effects of focused ultrasound on neuronal activity have been investigated since the 1920s. Low-intensity transcranial focused ultrasound can exert nondestructive mechanical pressure effects on cellular membranes and ion channels and has been shown to modulate the activity of peripheral nerves, spinal reflexes, the cortex, and even deep-brain nuclei, such as the thalamus. An efficient generator of focused ultrasound was designed, built, and successfully operated in the 1940s in the United States (13). Application of the focused supersonic beam was suggested whereby it should be possible to further increase the focal effects in the brain, with a corresponding decrease or elimination of complicating surface injury.

Interest in focused ultrasound ablation of tumors increased with subsequent advances in medical imaging and ultrasound technology. Extensive developments in the 1950s led to applications in clinical treatments of neurologic disorders. In particular, high-intensity ultrasound and ultrasound visualization were accomplished stereotaxically with a Cincinnati precision milling machine used to perform accurate ablation of brain tumors (02). Based on earlier successes, a computer-controlled focus ultrasound system guided by B-mode ultrasound, “The Candy machine,” was engineered in the 1970s to treat patients with brain tumors. This device could not be used through the skull, and its application required a craniectomy. The results were controversial, although the safety and feasibility of the procedure were demonstrated (06). The first commercially focused ultrasound machine, called the Sonablate 200, was developed by Focal Surgery Inc. and launched in Europe in 1994 after receiving CE approval in Europe, bringing a first medical validation of the technology for benign prostatic hyperplasia.

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