经颅超声在帕金森病治疗中的应用

The Application of Transcranial Ultrasound in The Treatment of Parkinson’s Disease

帕金森病是仅次于阿尔茨海默病的第二大常见神经退行性疾病,临床常用的治疗方法为药物治疗和神经外科手术。然而,目前尚无确切的方法阻止疾病的发展,新的治疗方案亟待探索。超声波因其具有非侵入性、高空间分辨率和高穿透性的特点,现已被广泛关注并用于帕金森病的治疗之中。近些年兴起的磁共振成像(MRI)引导聚焦超声消融技术、MRI引导聚焦超声开放血脑屏障给药技术、低强度聚焦超声调控技术和声遗传技术都已经在临床研究或临床前动物模型中取得可喜的成果。本文从以上4个方面综述近5年经颅超声技术在帕金森病治疗中的主要进展,并对其中的一些科学问题进行了探讨,以期为研究帕金森病发病机制和治疗方案的同行提供参考。

Parkinson’s disease(PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The commonly used treatments for PD include drug therapy and neurosurgery. At present, there is no definite method to prevent the development of the disease and new treatment schemes need to be explored. Ultrasound has been widely concerned and used as one of the treatment methods for PD due to its non-invasive, high spatial resolution and high penetrability characteristics. In recent years, MRI-guided focused ultrasound(MRg FUS) ablation technology, MRg FUS open blood brain barrier drug delivery technology, low-intensity focused ultrasound stimulation technology and sonogenetics have all achieved promising results in clinical research or preclinical animal models. MRg FUS ablation surgery is generally used to ablate unilateral nuclei to treat PD motor symptoms. This surgery has the advantages of non-invasiveness, small damage and quick effect, which shows a good application prospect in the treatment of PD. The blood brain barrier is a major obstacle for the effective delivery of macromolecule drugs to the brain. MRg FUS coupled with microbubbles can temporarily open the blood brain barrier, allowing drugs to enter the target area. The MRg FUS open blood brain barrier drug delivery technology has shown good therapeutic effect in PD animal models, its safety and reversibility have been preliminarily proved in human experiments. However, several key problems, such as effective ultrasound parameters, optimal microbubble size and administration dose, need to be resolved before clinical application. Low-intensity focused ultrasound stimulation technology is an emerging treatment method in recent years. It has demonstrated neuromodulation and neuroprotection functions in PD animal model studies, which can reverse animal movement disorders. low-intensity focused ultrasound stimulation is a potential treatment option for PD, but it also faces the problem of unstandardized treatment parameters. Sonogenetics is a new technology developed based on focused ultrasound, which is controllable in terms of spatiotemporal resolution and cell type. Several ultrasound-sensitive ion channels have been discovered, but whether these ion channels can be expressed in the human body and the related safety issues remain to be verified. This technology is currently in the early research stage and has great potential for development. The main progress of transcranial ultrasound in the treatment of PD in recent five years from the above four aspects are reviewed and some scientific problems are discussed in this paper, hoping to provide certain reference and help for the study of the pathogenesis and treatment of PD.