Evidence map›Paper›PMID 40450507›Full record

ArticleUltrasound in medicine & biology2025

Response of Serum-Isolated Extracellular Vesicles to Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Alina R Kline-Schoder, Fotios N Tsitsos, Alec J Batts, Melody R DiBenedetto, Keyu Liu, Sua Bae, Elisa E Konofagou

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Ultrasound in medicine & biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Alina R Kline-SchoderDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Fotios N TsitsosDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Alec J BattsDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Melody R DiBenedettoDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Keyu LiuDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Sua BaeDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Elisa E KonofagouDepartment of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Radiology, Columbia University, New York, NY, USA; Department of Neurological Surgery, Columbia University, New York, NY, USA. Electronic address: ek2191@columbia.edu.

Funding

Assessment of Ultrsound-facilitated Neurotherapeutics in Alzheimer's DiseaseR01AG038961 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI KONOFAGOU, ELISA E. · 2011 to 2020
$5.1M
Optimization of ultrasound-facilitated blood-brain barrier openingR01EB009041 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI KONOFAGOU, ELISA E. · 2008 to 2017
$4.4M
Assessment of ultrasound-facilitated neurotherapeutics in Alzheimer's diseaseR56AG038961 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KONOFAGOU, ELISA E. · 2023 to 2024
$1.6M
NIA NIH HHS R01 AG038961NIA NIH HHS R56 AG038961NIBIB NIH HHS R01 EB009041
6 · The paper itself

Abstract

objectiveTo characterize the response of extracellular vesicles (EV) in the serum of mice and Alzheimer's disease (AD) patients following focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening (FUS-BBBO) as a means to improve liquid biopsy.

methodsBlood was collected from C57BL/6 mice before, and one hour after FUS-BBBO, and from AD patients before, one hour after, and three days after FUS-BBBO. EVs were isolated from serum using the Exoquick precipitation solution and their concentration was quantified using nanoparticle tracking analysis. The transcriptomic and proteomic content of EVs from mice was assessed using RNA sequencing and mass spectrometry protein analysis respectively. Additionally, the release of EVs in mice was inhibited using the GW4869 drug to assess the role of EVs in the restoration of the BBB. Finally, the biomarker content of EVs in AD patients was detected using a Luminex multiplex assay.

resultsWe observed a 164±85% (95% confidence interval: 78.998 - 249.202) increase in murine EV concentration one hour after treatment, as well as an increase in EV RNA associated with FUS-BBBO neuroimmunotherapy. Inhibition of EVs reduced the inflammatory response and BBBO volume in mice. Patient EV concentration also increased one hour after treatment and was dependent on the volume of BBB opening three days post-treatment. Furthermore, EV isolation was found to significantly enhance (p<0.05) the detection of FUS-BBBO-induced amplification of AD and CNS biomarkers such as GFAP, beta-amyloid 42 and phosphorylated tau 181, exhibiting on average a 1.2 times higher log-fold change in biomarker levels in isolated EVs compared to total serum.

conclusionOverall, we hereby present the first evidence of altered murine and AD patient EV concentration and content in response to FUS-BBBO, providing evidence of EVs' role within FUS-BBBO neuroimmunotherapy as well as their utility in improving FUS-BBBO biomarker amplification. Our results pave the way for clinical applications of EV-based liquid biopsy in patients with neurodegenerative diseases following FUS-BBBO, as a way of noninvasively monitoring disease progression.

Indexed as

Alzheimer DiseaseBlood-Brain BarrierExtracellular VesiclesAnimalsBiomarkersDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLBiomarkersBiomarkersBlood-brain barrierExtracellular vesiclesFocused ultrasoundImmunotherapyLiquid biopsy

Identifiers

PMID40450507
PMCPMC12229771

What Socratic holds

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Registered trials

None linked

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 Socratic graph.