Evidence map›Paper›PMID 33693781›Full record

ArticleNeuro-oncology2021

MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors.

Ying Meng, Christopher B Pople, Suganth Suppiah, Maheleth Llinas, Yuexi Huang, Arjun Sahgal, James Perry, Julia Keith, Benjamin Davidson, Clement Hamani and 7 more

2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 99 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 2 pooled it
8.0field-weighted citation impact, top 1% 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.

NCT03616860 nacompletednot on this map

Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of High Grade Glioma in Patients Undergoing Standard Chemotherapy

TypeinterventionalSponsorInSightecRan2018 to 2023Enrolled14ConditionsGlioblastomaArmsFocused Ultrasound (FUS) BBB Disruption
NCT03739905 nacompletednot on this map

A Phase IIa Study to Evaluate the Safety and Efficacy of Blood-Brain Barrier (BBB) Opening Using Transcranial MR-Guided Focused Ultrasound in Patients With Alzheimer's Disease

TypeinterventionalSponsorInSightecRan2018 to 2025Enrolled35ConditionsAlzheimer DiseaseArmsBlood Brain Barrier (BBB) Disruption
3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.

  1. Pooled it
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  4. Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood-Brain Barrier Opening.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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  12. Focused ultrasound for brain metastases.Neuro-oncology advances · 2026
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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Ying MengSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0003-3180-2404
Christopher B PopleSunnybrook Research Institute, Toronto, Ontario, Canada.
Suganth SuppiahDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Maheleth LlinasSunnybrook Research Institute, Toronto, Ontario, Canada.
Yuexi HuangSunnybrook Research Institute, Toronto, Ontario, Canada.
Arjun SahgalSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0001-7991-8970
James PerrySunnybrook Research Institute, Toronto, Ontario, Canada.
Julia KeithSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0003-1519-6731
Benjamin DavidsonSunnybrook Research Institute, Toronto, Ontario, Canada.
Clement HamaniSunnybrook Research Institute, Toronto, Ontario, Canada.
Yutaka AmemiyaSunnybrook Research Institute, Toronto, Ontario, Canada.
Arun SethSunnybrook Research Institute, Toronto, Ontario, Canada.
Hon LeongSunnybrook Research Institute, Toronto, Ontario, Canada.
Chinthaka C HeynSunnybrook Research Institute, Toronto, Ontario, Canada.
Isabelle AubertSunnybrook Research Institute, Toronto, Ontario, Canada.ORCID 0000-0001-5163-9961
Kullervo HynynenSunnybrook Research Institute, Toronto, Ontario, Canada.
Nir LipsmanSunnybrook Research Institute, Toronto, Ontario, Canada.
University of Toronto · CASunnybrook Hospital · CASunnybrook Health Science Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLiquid biopsy is promising for early detection, monitoring of response, and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood from brain tumors, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized that MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy.

methodsNine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening (BBBO) alone (NCT03739905).

resultsBrain regions averaging 7.8 ± 6.0 cm3 (range 0.8-23.1 cm3) were successfully treated within 111 ± 39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6 ± 1.2-fold, P < .01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2 ± 1.9-fold, P < .01), and brain-specific protein S100b (1.4 ± 0.2-fold, P < .01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease- and post-BBBO-specific, in keeping with our hypothesis. We also found cfDNA-mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbor the tumor mutation.

conclusionsThis first-in-human proof-of-concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.

Indexed as

Brain NeoplasmsMagnetic Resonance ImagingBiomarkersHumansLiquid BiopsyProspective StudiesBiomarkersblood-brain barrierbrain tumorfocused ultrasoundglioblastomaliquid biopsy

Identifiers

PMID33693781
PMCPMC8485448
OpenAlexW3134763185

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.