Evidence map›Paper›PMID 29133392›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model.

Tao Sun, Yongzhi Zhang, Chanikarn Power, Phillip M Alexander, Jonathan T Sutton, Muna Aryal, Natalia Vykhodtseva, Eric L Miller, Nathan J McDannold

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 1 pooled it
12.4field-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.

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

131 citing papers in PubMed, 1 synthesis or guideline pooled it, 244 citations in OpenAlex.

  1. Pooled it
  2. Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Trial
  3. Article
  4. Ultrasound-responsive composite hydrogels: Design rules for spatiotemporally controlled drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
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  17. Review
  18. Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024
    Review
  19. Review
  20. Article

71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Tao SunFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; taosun@bwh.harvard.edu.
Yongzhi ZhangFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Chanikarn PowerFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Phillip M AlexanderFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Jonathan T SuttonFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Muna AryalFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Natalia VykhodtsevaFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Eric L MillerDepartment of Electrical and Computer Engineering, Tufts University, Medford, MA 02155.
Nathan J McDannoldFocused Ultrasound Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Brigham and Women's Hospital · USHarvard University · USTufts University · US

Funding

Ultrasound-induced blood-brain/tumor barrier disruption in brain metastasesP01CA174645 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI JOLESZ, FERENC A, MCDANNOLD, NATHAN J. · 2013 to 2017
$6.2M
NCI NIH HHS P01 CA174645
6 · The paper itself

Abstract

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood-brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.3 kHz. Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma. These results confirmed the ability of the controller to modulate the drug delivery dosage within a therapeutically effective range, while improving safety control. It can be readily implemented clinically and potentially applied to other cavitation-enhanced ultrasound therapies.

Indexed as

AcousticsAnimalsAntibiotics, AntineoplasticBlood-Brain BarrierBrain NeoplasmsCarbocyaninesCorpus StriatumDisease Models, AnimalDoxorubicinDrug Delivery SystemsFluorescent DyesGliomaHippocampusLuminescent ProteinsMagnetic Resonance ImagingMaleAntibiotics, AntineoplasticCarbocyaninesCY5.5 cyanine dyeDoxorubicinFluorescent Dyesfluorescent protein 583liposomal doxorubicinLuminescent ProteinsPolyethylene Glycolsacoustic cavitationblood–brain barrierdrug deliveryfocused ultrasoundtreatment control

Identifiers

PMID29133392
PMCPMC5715774
OpenAlexW2768295381

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.