Pitt Shield

Glymphatics Visualization after Focused Ultrasound-Induced Blood-Brain Barrier Opening in Humans.

Authors: Meng Y, Abrahao A, Heyn CC, Bethune AJ, Huang Y, Pople CB, Aubert I, Hamani C, Zinman L, Hynynen K, Black SE, Lipsman N

It is currently unclear whether the glymphatic system, a brain-wide interstitial fluid-cerebrospinal fluid exchange described in rodents, exists in humans. Focal blood-brain barrier disruption using magnetic resonance-guided focused ultrasound allows parenchymal penetration of gadobutrol contrast, creating an opportunity to study glymphatics in vivo noninvasively. We describe patterns of contrast distribution in the perivascular space, subarachnoid space, and space surrounding large veins draining toward the dural sinuses on fluid-attenuated inversion recovery in subjects with Alzheimer disease and amyotrophic lateral sclerosis. This is the first evidence suggesting glymphatic efflux persists in humans. It's relevance to proteinopathies and drug delivery is discussed. ANN NEUROL 2019;86:975-980.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To visualize and assess glymphatic pathways in humans following focused ultrasound-induced blood–brain barrier opening.
Animal model / Human subject Human (Homo sapiens); strain: N/A; age: not specified; sex: not specified
Disease model Alzheimer's disease
Cargo name and characteristics Focused ultrasound (FUS): a noninvasive physical modality used to transiently and focally open the blood–brain barrier in humans to enable glymphatic visualization; not a molecular cargo but an energy-based experimental intervention.
Route of administration transcranial focused ultrasound

Outcomes and Safety

Summary of Outcomes Focused ultrasound-induced blood–brain barrier opening in humans enables visualization of glymphatic pathways.

Brain Region

Visualization unavailable

Ultrasound Parameters

FUS Mode pulsed

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