A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer’s disease

• Published in: Ultrasonography (Seoul, Korea) Vol. 40; no. 4; pp. 512 - 519
• Main Authors: Jeong, Hyeonseok, Im, Jooyeon Jamie, Park, Jong-Sik, Lee, Wonhye, Yoo, Seung-Schik, Song, In-Uk, Chung, Yong-An
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Ultrasound in Medicine 01.10.2021; 대한초음파의학회
• Subjects: Acoustics; Alzheimer's disease; Bandwidths; Brain; cognitive function; Contrast agents; Dementia; low-intensity transcranial focused ultrasound; Magnetic resonance imaging; Medical imaging; Memory; Mental disorders; Neuropsychology; Original; Patients; regional cerebral metabolic rate of glucose; Tomography; Ultrasonic imaging; 방사선과학; United States > US; Low-intensity transcranial focused ultrasound; Regional cerebral metabolic rate of glucose; Alzheimer’s disease; Cognitive function
• ISSN: 2288-5919; 2288-5943
• DOI: 10.14366/usg.20138

Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.