a Physical Sciences Platform , Sunnybrook Research Institute , Toronto , ON , Canada.
b Department of Medical Biophysics , University of Toronto , Toronto , ON , Canada.
Expert Opin Drug Deliv. 2019 Feb;16(2):129-142. doi: 10.1080/17425247.2019.1567490. Epub 2019 Jan 29.
Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma.
Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behavior analyses. Here we provide an overview of the factors that affect the safety profile of these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks.
There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention.
治疗几种脑部疾病都很复杂，因为有颅骨和血脑屏障（BBB）的存在。聚焦超声（FUS）和微泡（MB）介导的 BBB 治疗是一种微创方法，可短暂增加靶向脑区血管的通透性。它可以用作一般的输送系统，以增加脑实质中治疗剂的浓度。
在过去的二十年中，已经通过各种成像、组织学、生化分析和行为分析方法来研究使用 FUS+MB 将药物输送穿过 BBB 的安全性。在这里，我们提供了影响这些治疗安全性的因素概述，描述了控制 FUS+MB 治疗的方法，并讨论了为评估治疗风险提供信息的数据。
仍需要评估与临床相关的治疗策略（包括有和没有治疗剂输送的重复 FUS+MB 治疗）相关的风险。此外，努力开发指标，以便可以在研究之间轻松比较 FUS+MB 治疗，将有助于更快地就该干预措施的风险达成共识。
