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. 2020 Oct 7:14:593672.
doi: 10.3389/fnhum.2020.593672. eCollection 2020.

β-Amyloid Plaque Reduction in the Hippocampus After Focused Ultrasound-Induced Blood-Brain Barrier Opening in Alzheimer's Disease

Pierre-François D'Haese  1   2   3   4 , Manish Ranjan  1   5 , Alexander Song  6 , Marc W Haut  1   7 , Jeffrey Carpenter  1   4 , Gerard Dieb  1   4 , Umer Najib  1   8 , Peng Wang  1   4 , Rashi I Mehta  1   4 , J Levi Chazen  9 , Sally Hodder  10 , Daniel Claassen  6 , Michael Kaplitt  11 , Ali R Rezai  1   5
Affiliations

β-Amyloid Plaque Reduction in the Hippocampus After Focused Ultrasound-Induced Blood-Brain Barrier Opening in Alzheimer's Disease

Pierre-François D'Haese et al. Front Hum Neurosci. .

Abstract

The blood-brain barrier (BBB) limits therapeutic delivery in Alzheimer's disease (AD) and other neurological disorders. Animal models have demonstrated safe BBB opening and reduction in β-amyloid plaque with focused ultrasound (FUS). We recently demonstrated the feasibility, safety, and reversibility of FUS-induced BBB opening in the hippocampus and entorhinal cortex in six participants with early AD. We now report the effect of BBB opening with FUS treatment on β-amyloid plaque. Six participants underwent 18F-Florbetaben PET scan at baseline and 1 week after the completion of the third FUS treatment (60 days interval). PET analysis comparing the hippocampus and entorhinal cortex in the treated and untreated hemispheres revealed a decrease in the ratio of 18F-Florbetaben ligand binding. The standard uptake value ratios (SUVr) reduction ranged from 2.7% to 10% with an average of 5.05% (±2.76) suggesting a decrease in β-amyloid plaque.

Keywords: Alzheimer’s disease; FUS; blood-brain barrier; focused ultrasound; hippocampus; β-amyloid reduction.

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Figures

FIGURE 1
FIGURE 1
One of the targets for one of the participants as a green square in the left hippocampus, overlaid on the baseline sagittal T1-weighted MRI.
FIGURE 2
FIGURE 2
Timeline of the experiments. The pair of PET and MRI images is acquired at baseline and 7 days after the third and last sonication treatment. Cognitive state of the patient is assessed at baseline, 7, 30, and 90 days after the last sonication. Each patient undergoes three sonication treatments 2 weeks apart.
FIGURE 3
FIGURE 3
Post-contrast axial T1-weighted images. (A) Baseline; (B) Immediate post-FUS treatment demonstrating contrast enhancement (arrows) at target sites, indicating focal BBB opening; (C) 24-h post-sonication images show resolution of parenchymal contrast enhancement, indicating BBB closure.
See this image and copyright information in PMC

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