@article{caba259c2f8b4d228874ad6317e731d6,
title = "Blood–brain barrier opening in Alzheimer{\textquoteright}s disease using MR-guided focused ultrasound",
abstract = "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{\textquoteright}s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer{\textquoteright}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{\textquoteright}s disease.",
author = "Nir Lipsman and Ying Meng and Bethune, {Allison J.} and Yuexi Huang and Benjamin Lam and Mario Masellis and Nathan Herrmann and Chinthaka Heyn and Isabelle Aubert and Alexandre Boutet and Smith, {Gwenn S.} and Kullervo Hynynen and Black, {Sandra E.}",
note = "Funding Information: Role of funding source. InSightec, the manufacturer of the ExAblate device used in this study, was the regulatory sponsor and had no role in study design, data collection, analysis, or interpretation. This study was funded by a grant from the Focused Ultrasound Foundation, a non-profit organization that funds research into clinical applications of ultrasound. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: This study was supported by the Focused Ultrasound Foundation and Sunnybrook Foundation. The authors would like to thank Ruby Endre and Garry Detzler for their technical support in the study, and patients and their families for their involvement and contributions. N.L. is grateful for the philanthropic gifts to the Sunnybrook Foundation, Sunnybrook Research Institute, and Harquail Centre for Neuromodulation. S.E.B. is grateful for the financial support from the Sunnybrook Research Institute, the Brill Chair, Department of Medicine at University of Toronto, Sunnybrook Foundation, and the Toronto Dementia Research Alliance. M.M. acknowledges financial support from the Department of Medicine at SHSC, University of Toronto, and Sunnybrook Foundation. N.H. acknowledges financial support from the Lewar Chair, and Department of Psychiatry at SHSC and University of Toronto. B.L. was supported by the LC Campbell Foundation and the Slaight Foundation. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04529-6",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}