Transcranial Ultrasound Innovations Ready for Broad Clinical Application

Abstract

Brain diseases are one of the most important problems in our rapidly ageing society. Currently, there are not many effective medications and surgical options are limited due to invasiveness and non-invasive brain stimulation techniques cannot be well targeted and cannot access deep brain areas. A novel therapy is transcranial ultrasound which allows a variety of treatments without opening of the skull. Recent technological developments generated three revolutionary options including 1) targeted non-invasive surgery, 2) highly targeted drug, antibody, or gene therapy via local opening of the blood-brain barrier, and 3) highly targeted brain stimulation to improve pathological brain functions. This progress report summarizes the current state of the art for clinical application and the results of recent patient investigations.

Keywords: brain therapy; neuropsychiatric disease; ultrasound.

Figure 1

Principle of a helmet system with 1024 ultrasound transducer elements for focal surgery or focal blood–brain barrier (BBB) opening. Reproduced with permission. Copyright INSIGHTEC (www.insightec.com).

Figure 2

Ultrasound surgery of the right unilateral thalamus (white arrow) of a patient with essential tremor performed with a focused ultrasound helmet system (compare Figure 1). Lesion generation (day 1) and subsequent healing are shown over a period of 90 days. Adapted with permission.^{[ 7 ]} Copyright 2013, Elsevier.

Figure 3

Blood–brain barrier opening of a larger brain area via sonication of a 3 × 3 grid consisting of 3 × 3 × 6 mm cubes.^{[ 27 ]} Extravasation of contrast agent from the blood to the brain is visible and corresponds to the precisely sonicated grid pattern (yellow square). Reproduced under the terms of the CC‐BY‐4.0 International license.^{[ 27 ]} Copyright 2019, Springer Nature.

Figure 4

Setting with the transcranial pulse stimulation system (TPS) for individualized brain stimulation therapy.^{[ 41 ]} With TPS transcranial ultrasound can be targeted with millimeter precision to every superficial and deep area of the patient's brain.