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Neuroimage. 2019 Oct 15;200:275-280. doi: 10.1016/j.neuroimage.2019.06.060. Epub 2019 Jun 26.

Resting state functional connectivity changes after MR-guided focused ultrasound mediated blood-brain barrier opening in patients with Alzheimer's disease.

Author information

1
Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
2
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
3
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
4
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
5
Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
6
Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
7
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Canada.
8
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
9
Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. Electronic address: nir.lipsman@sunnybrook.ca.

Abstract

MR-guided focused ultrasound (MRgFUS) can temporarily permeabilize the blood-brain barrier (BBB), noninvasively, to allow therapeutics access to the central nervous system. However, its secondary and potential neuromodulation effects are not well understood. We aimed to characterize the functional impact of MRgFUS BBB opening in human subjects, based on the phase I trial in patients with Alzheimer's disease. We analyzed for changes in bilateral frontoparietal networks in resting state functional MRI from five subjects after BBB opening in the right frontal lobe. We found a transient functional connectivity decrease within only the ipsilateral frontoparietal network that was recovered by the next day. Additionally, baseline to month three comparisons did not reveal any significant differences from matched-controls from the Alzheimer's Disease Neuroimaging Initiative. Overall, MRgFUS may transiently affect neurologic function, but the functional organization is restored at one day and remains unchanged at three months. This first in human data has implications for the development of MRgFUS as a drug delivery platform to pathologic brain tissue and potential use for non-invasive neuromodulation.

KEYWORDS:

Blood-brain barrier; Blood-brain barrier opening; Functional connectivity; MR-Guided focused ultrasound; Resting state functional MRI

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