Received: September 4, 2020; Accepted: January 16, 2021. Published online: January 16, 2021.
ABSTRACT
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, regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD.
Methods: After the approval of institutional review board, four patients with AD received tFUS to the hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. The 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 between before and after the 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, middle cingulate gyrus, and fusiform gyrus was increased after tFUS (p < 0.005). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive functions 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 functions in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.
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