Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada; email:
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5, Canada.
Annu Rev Biomed Eng. 2021 Jul 13;23:89-113. doi: 10.1146/annurev-bioeng-062117-121238. Epub 2021 Mar 22.
Specialized features of vasculature in the central nervous system greatly limit therapeutic treatment options for many neuropathologies. Focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels. With the wide range of therapeutic agents that can be delivered using this approach and the growing clinical need, focused ultrasound and microbubble (FUS+MB) exposure in the brain has entered human testing to assess safety. This review outlines the use of FUS+MB-mediated cerebrovascular permeability enhancement as a drug delivery technique, details several technical and biological considerations of this approach, summarizes results from the clinical trials conducted to date, and discusses the future direction of the field.
中枢神经系统血管的特殊结构极大地限制了许多神经病理学的治疗选择。聚焦超声联合循环微泡可用于短暂且非侵入性地增加脑血管通透性，具有很高的空间精度。在超声处理后的几分钟到几个小时内，药物可以全身给药，使药物外渗到目标脑区并发挥治疗作用，之后通透性恢复到基线水平。由于可以使用这种方法递送广泛的治疗剂，并且临床需求不断增长，因此聚焦超声和微泡（FUS+MB）在大脑中的暴露已进入人体测试以评估安全性。本文综述了 FUS+MB 介导的脑血管通透性增强作为一种药物递送技术的应用，详细介绍了该方法的几个技术和生物学方面的考虑因素，总结了迄今为止进行的临床试验结果，并讨论了该领域的未来发展方向。
