Evidence map›Paper›PMID 25438846›Full record

ArticleUltrasound in medicine & biology2015

Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis.

Kenneth B Bader, Matthew J Gruber, Christy K Holland

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Ultrasound in medicine & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. 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
  5. Low-intensity ultrasound lysis of amyloid microclots in a lab-on-chip model.Frontiers in bioengineering and biotechnology · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Sonothrombolysis for Ischemic Stroke.Journal of cardiovascular development and disease · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Kenneth B BaderDivision of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA. Electronic address: kenneth.bader@uc.edu.
Matthew J GruberBiomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA.
Christy K HollandDivision of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA; Biomedical Engineering Program, University of Cincinnati, Cincinnati, Ohio, USA.
University of Cincinnati · US

Funding

Ultrasound-Assisted Thrombolysis for Stroke TherapyR01NS047603 · NINDS · UNIVERSITY OF CINCINNATI · PI HOLLAND, CHRISTY K. · 2004 to 2018
$7.5M
NINDS NIH HHS R01 NS047603
6 · The paper itself

Abstract

The use of ultrasound and microbubbles as an effective adjuvant to thrombolytics has been reported in vitro, ex vivo and in vivo. However, the specific mechanisms underlying ultrasound-enhanced thrombolysis have yet to be elucidated. We present visual observations illustrating two mechanisms of ultrasound-enhanced thrombolysis: acoustic cavitation and radiation force. An in vitro flow model was developed to observe human whole blood clots exposed to human fresh-frozen plasma, recombinant tissue-type plasminogen activator (0, 0.32, 1.58 or 3.15 μg/mL) and the ultrasound contrast agent Definity (2 μL/mL). Intermittent, continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure) was used to insonify the perfusate. Ultraharmonic emissions indicative of stable cavitation were monitored with a passive cavitation detector. The clot was observed with an inverted microscope, and images were recorded with a charge-coupled device camera. The images were post-processed to determine the time-dependent clot diameter and root-mean-square velocity of the clot position. Clot lysis occurred preferentially surrounding large, resonant-sized bubbles undergoing stable oscillations. Ultraharmonic emissions from stable cavitation were found to correlate with the lytic rate. Clots were observed to translate synchronously with the initiation and cessation of the ultrasound exposure. The root-mean-square velocity of the clot correlated with the lytic rate. These data provide visual documentation of stable cavitation activity and radiation force during sub-megahertz sonothrombolysis. The observations of this study suggest that the process of clot lysis is complex, and both stable cavitation and radiation force are mechanistically responsible for this beneficial bio-effect in this in vitro model.

Indexed as

Blood CellsBlood CoagulationHumansMechanical ThrombolysisRadiation DosageUltrasonic TherapyAcoustic cavitationAcute ischemic strokeUltrasoundUltrasound contrast agents

Identifiers

PMID25438846
PMCPMC4258471
OpenAlexW1972538928

What OpenQuestion holds

Textmetadata
LicenceTDM
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.