Pitt Shield

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

Authors: D'Haese PF, Ranjan M, Song A, Haut MW, Carpenter J, Dieb G, Najib U, Wang P, Mehta RI, Chazen JL, Hodder S, Claassen D, Kaplitt M, Rezai AR

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 <sup>18</sup>F-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 <sup>18</sup>F-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.

Introduction

Purpose Other
Study Objective To evaluate whether MR-guided focused ultrasound–induced blood–brain barrier opening in the hippocampus and entorhinal cortex reduces β-amyloid plaque burden in patients with early Alzheimer’s disease.
Animal model / Human subject Human (Homo sapiens); strain: N/A; age: 55-73 years (participants with early Alzheimer’s disease); sex: 5 female, 1 male
Disease model Alzheimer's disease
MRI or image guidance method MR-guided
Targeted brain region(s) Hippocampus And Entorhinal Cortex

Outcomes and Safety

Summary of Outcomes MR-guided focused ultrasound produced reduced β-amyloid PET signal in the treated region with no clinically meaningful cognitive changes observed. The paper did not test multiple FUS parameter sets beyond these targeted hippocampus/EC sonications.
Safety-related matter The study reports that FUS-induced BBB opening was feasible, safe, and reversible (contrast enhancement resolved within 24 hours), formal cognitive assessments showed no clinically meaningful changes, and no adverse effects were reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument ExAblate Neuro Type 2 system (Insightec)
FUS Frequency 220 kHz
Duration of a single FUS session 90 s
Focal Characteristics focal depth: None, focal length: None, aperture size: None
Treatment frequency multiple sessions

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