Jeong Hyeonseok, Im Jooyeon Jamie, Park Jong-Sik, Na Seung-Hee, Lee Wonhye, Yoo Seung-Schik, Song In-Uk, Chung Yong-An
Department of Nuclear Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Neurology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Ultrasonography. 2021 Oct;40(4):512-519. doi: 10.14366/usg.20138. Epub 2021 Jan 16.
Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD.
After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS.
The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported.
These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.
低强度经颅聚焦超声（tFUS）因其在阿尔茨海默病（AD）中的潜在治疗作用而受到越来越多的关注。虽然临床前研究已显示低强度tFUS在AD模型中具有有前景的治疗效果，但其在人体中的疗效和安全性仍不明确。在这项初步研究中，我们调查了低强度tFUS对AD患者血脑屏障开放、局部脑葡萄糖代谢率（rCMRglu）和认知的影响。
在获得机构审查委员会批准后，4例AD患者在静脉注射微泡超声造影剂后立即接受海马区的tFUS治疗。以低于血脑屏障开放阈值的压力水平进行低强度超声处理。患者在tFUS治疗前后接受脑磁共振成像、18F-氟-2-脱氧葡萄糖正电子发射断层扫描和神经心理学评估。进行全脑体素水平的配对t检验以比较tFUS前后的rCMRglu。
如预期的那样，超声处理在T1动态对比增强磁共振成像上未显示血脑屏障开放的证据。tFUS后，额上回（P<0.001）、扣带回中部（P<0.001）和梭状回的rCMRglu增加（P=0.001）。tFUS后患者在记忆、执行和整体认知功能测量方面有轻度改善。未报告不良事件。
这些结果表明，低强度tFUS海马区超声处理可能对AD患者的脑葡萄糖代谢和认知功能有有益影响。需要进一步的大型研究来证实tFUS在AD中的治疗效果。
