Focused ultrasound treatment for central nervous system disease: neurosurgeon's perspectives

Abstract

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21^st century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson's disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a pre-clinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.

Keywords: Central nervous system; Disease; Focus; Non-invasive; Ultrasound.

Fig. 1

Procedural steps for magnetic resonance guided focused ultrasound treatment

Fig. 2

Magnetic resonance images after magnetic resonance guided focused ultrasound capsulotomy for obsessive compulsive disorder. Yellow circles indicate focal lesioning of target area

Fig. 3

Low intensity transcranial focused ultrasound sonication for non-invasive opening of blood brain barrier. Blue spot; trans-endothelial leakage of dye (Evans blue) after treatment. No injured vessels were found in treatment area on histological examination

Fig. 4

Trans-endothelial migration of mesenchymal stem cell (MSC) at the site of focused ultrasound sonication. A; site of sonication, B; difference of cell counts (PKH26 immunohistochemistry for mesenchymal stem cell staining, white arrow) between focused ultrasound treated area (ipsilateral, IL), and untreated area (contralateral, CL)

Fig. 5

Tendency of energy requirement during human clinical trials using focused ultrasound thermal ablation according to the skull volume and skull density ratio (SDR). Skulls with higher SDR and lower skull volume in treatment area have tendency to require less maximum energy for thermal ablation although there is no statistical significance due to small number of cases