Evidence map›Paper›PMID 36694943›Full record

ArticleBrain : a journal of neurology2023

Blood-brain barrier opening of the default mode network in Alzheimer's disease with magnetic resonance-guided focused ultrasound.

Ying Meng, Maged Goubran, Jennifer S Rabin, Melissa McSweeney, Julie Ottoy, Christopher B Pople, Yuexi Huang, Alexandra Storace, Miracle Ozzoude, Allison Bethune and 14 more

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04118764 (Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients), which is not on this map. Cited by 30 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 3 pooled it
6.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04118764 nacompletednot on this map

Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients

TypeinterventionalSponsorColumbia UniversityRan2020 to 2022Enrolled6ConditionsAlzheimer DiseaseArmsNeuronavigation-guided single-element focused ultrasound transducer, Definity, Magnetic Resonance Imaging (MRI) with or without gadolinium contrast agents, Positron Emission Tomography (PET), Amyvid
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  8. Passive cavitation imaging with pMedical physics · 2026
    Article
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  13. The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025
    Review
  14. Overview of Therapeutic Ultrasound Applications and Safety Considerations: 2024 Update.Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 4 countries.

Ying MengDivision of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.ORCID 0000-0003-3180-2404
Maged GoubranSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Jennifer S RabinSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.ORCID 0000-0003-4754-2221
Melissa McSweeneySunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Julie OttoySunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.ORCID 0000-0002-9879-7497
Christopher B PopleSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Yuexi HuangSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Alexandra StoraceSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Miracle OzzoudeSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Allison BethuneSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Benjamin LamSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Walter SwardfagerSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Chinthaka HeynSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Agessandro AbrahaoSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.ORCID 0000-0003-1142-2842
Benjamin DavidsonDivision of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Clement HamaniDivision of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Isabelle AubertSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.ORCID 0000-0001-5163-9961
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.ORCID 0000-0003-3930-4354
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Thomas K KarikariDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.ORCID 0000-0003-1422-4358
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, 405 30 Mölndal, Sweden.
Sandra E BlackSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Kullervo HynynenSunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Nir LipsmanDivision of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Sunnybrook Health Science Centre · CASahlgrenska University Hospital · SEKing's College London · GBUniversity of Pittsburgh · US

Funding

Ultrasound Therapy Delivery Through Intact SkullR01EB003268 · NIBIB · SUNNYBROOK & WOMEN'S COLL HLTH SCIS CTR · PI HYNYNEN, KULLERVO · 2003 to 2020
$8.2M
NIBIB NIH HHS R01 EB003268
6 · The paper itself

Abstract

The blood-brain barrier (BBB) protects the brain but is also an important obstacle for the effective delivery of therapeutics in Alzheimer's disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer's disease relevant pathology need to be better characterized. This study is an open-labelled single-arm trial (NCT04118764) to investigate the feasibility of modulating BBB permeability in the default mode network and the impact on cognition, amyloid and tau pathology as well as BBB integrity. Nine participants [mean age 70.2 ± 7.2 years, mean Mini-Mental State Examination (MMSE) 21.9] underwent three biweekly procedures with follow-up visits up to 6 months. The BBB permeability of the bilateral hippocampi, anterior cingulate cortex and precuneus was transiently increased without grade 3 or higher adverse events. Participants did not experience worsening trajectory of cognitive decline (ADAS-cog11, MMSE). Whole brain vertex-based analysis of the 18F-florbetaben PET imaging demonstrated clusters of modest SUVR reduction in the right parahippocampal and inferior temporal lobe. However, CSF and blood biomarkers did not demonstrate any amelioration of Alzheimer's disease pathology (P-tau181, amyloid-β42/40 ratio), nor did it show persistent BBB dysfunction (plasma PDGFRbeta and CSF-to-plasma albumin ratio). This study provides neuroimaging and fluid biomarker data to characterize the safety profile of MRgFUS BBB modulation in neurodegeneration as a potential strategy for enhanced therapeutic delivery.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAmyloid beta-PeptidesBiomarkersBlood-Brain BarrierDefault Mode NetworkHumansMagnetic Resonance SpectroscopyMiddle AgedPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkerstau Proteins18F-florbetaben PETAlzheimer’s diseasebiomarkersblood-brain barrierfocused ultrasound

Identifiers

PMID36694943
PMCPMC10226733
OpenAlexW4317915794

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.