论文标题：Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
期刊：
作者：Nir Lipsman et al
发表时间： 2018/07/25
数字识别码：10.1038/s41467-018-04529-6
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《自然-通讯》论文Blood–brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound发表的一项一期临床试验用无创、可逆的方式开放了五名阿尔茨海默症患者的血脑屏障。结果显示，操作流程很安全，但对聚焦超声改善阿尔茨海默症临床症状的功效尚无定论。
图1：核磁共振成像显示血脑屏障的开放和关闭。图源：Lipsman et al.
血脑屏障（BBB）会阻碍治疗药物到达脑部，而聚焦超声联合微泡技术可以有效开放血脑屏障，清除阿尔茨海默症动物模型脑中的淀粉样蛋白。此外，聚焦超声还能通过植入装置作用于脑瘤患者。
加拿大Sunnybrook健康明升体育app中心的Nir Lipsman及同事运用无创装置对五名轻到中度阿尔茨海默症患者（三名男性、两名女性）右侧大脑额叶的淀粉样蛋白聚集区域进行聚焦超声辐照。结果显示，这一操作能快速、可逆地开放五位患者的血脑屏障，并不会出现显著的不良反应。不过，患者的淀粉样蛋白成像标记和认知功能均未检测到明显的临床变化。
图2：[18F]-Florbetaben正电子发射断层扫描。a表示基准线，b表示声波降解法一周后的扫描状况 ，c表示血脑屏障破坏后显示出目标区域。图源：Alfonso Castro
结果显示该操作流程很安全，但能否有效清除淀粉样蛋白并改善认知功能仍需大规模研究加以证实。
摘要：Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer’s disease in a phase I safety trial. In all patients, the blood–brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood–brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [18F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer’s disease.
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