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  • [Ultrasonography.] A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease

    [Ultrasonography.] A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer's disease

    가톨릭대 / 정현석, 임주연, 정용안*

  • 출처
    Ultrasonography.
  • 등재일
    2021 Oct
  • 저널이슈번호
    40(4):512-519. doi: 10.14366/usg.20138. Epub 2021 Jan 16.
  • 내용

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    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, 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.

     

     

     

    Affiliations

    Hyeonseok Jeong  1   2   3 , Jooyeon Jamie Im  1   2 , Jong-Sik Park  2 , Seung-Hee Na  2 , Wonhye Lee  4 , Seung-Schik Yoo  4 , In-Uk Song  2 , Yong-An Chung  1   3
    1 Department of Nuclear Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    2 Department of Neurology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    3 Department of Radiology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    4 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

  • 키워드
    Alzheimer’s disease; Cognitive function; Low-intensity transcranial focused ultrasound; Regional cerebral metabolic rate of glucose.
  • 연구소개
    최근 알츠하이머병에서 약물 치료 외의 대안으로 비침습적 뇌자극 치료법이 (예: 경두개직류전기자극술, 경두개자기장자극술, 저강도집중초음파자극술 등) 많이 연구되고 있다. 본 연구는 저강도집중초음파자극을 참여 대상자 뇌의 해마에 직접 공여한 최초의 탐색 임상 연구로, 저강도집중초음파 뇌자극 치료의 안정성 및 임상적 유용성을 신경심리검사, 뇌자기공명영상, 뇌포도당양전자단층촬영술 등을 통해 평가하였다. 연구 결과는 뇌혈관장벽 개통을 위한 역치 미만의 저강도집중초음파가 안전하게 전달되었으며 알츠하이머병 환자의 뇌 포도당 대사 및 인지 기능을 향상 효과가 있음을 시사하였다. 결론적으로 대뇌피질 및 심뇌 영역 모두에 대한 새로운 비침습적 뇌자극 도구 역할을 할 수 있을 것으로 기대한다.
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