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Cited by 52Ultrasound and Hyperthermia ApplicationsBarrier Structure and Function StudiesPhotoacoustic and Ultrasonic Imaging

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Microbubble formulation influences inflammatory response to focused ultrasound exposure in the brain

Open access
McMahon, Dallan, Lassus, Anne, Gaud, Emmanuel, Jeannot, Victor, Hynynen, Kullervo·2020·Scientific Reports
DOI 10.1038/s41598-020-78657-9PMC PMC7725832
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Abstract

Focused ultrasound and microbubble (FUS + MB)-mediated blood–brain barrier (BBB) permeability enhancement can facilitate targeted brain-drug delivery. While controlling the magnitude of BBB permeability enhancement is necessary to limit tissue damage, little work has attempted to decouple these concepts. This work investigated the relationship between BBB permeability enhancement and the relative transcription of inflammatory mediators 4 h following sonication. Three microbubble formulations, Definity, BG8774, and MSB4, were compared, with the dose of each formulation normalized to gas volume. While changes in the transcription of key proinflammatory mediators, such as Il1b, Ccl2, and Tnf, were correlated to the magnitude of BBB permeability enhancement, these correlations were not independent of microbubble formulation; microbubble size distribution may play an important role, as linear regression analyses of BBB permeability magnitude versus differential gene expression for these proinflammatory mediators revealed significantly greater slopes for MSB4, a monodisperse microbubble with mean diameter of 4 μm, compared to Definity or BG8774, both polydisperse microbubbles with mean diameters below 2 μm. Additionally, the function of an acoustic feedback control algorithm, based on the detection threshold of ultraharmonic emissions, was assessed. While this control strategy was effective in limiting both wideband emissions and red blood cell extravasation, microbubble formulation was found to influence the magnitude of BBB leakage and correlations to acoustic emissions. This work demonstrates that while the initial magnitude of FUS + MB-mediated BBB permeability enhancement has a clear influence on the subsequent inflammatory responses, microbubble characteristics influence these relationships and must also be considered.

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Metadata

Authors
McMahon, D., Lassus, A., Gaud, E., Jeannot, V., & Hynynen, K.
Affiliations
  • University of Toronto (CA)
  • Bracco (Switzerland) (CH)
Corresponding author
McMahon, Dallan
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-12-09
Volume
10
Issue
1
Pages
21534-21534
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-78657-9
PMC
PMC7725832
OpenAlex
W3111969895
Cited by
52
References
3
Citations by year
2026: 10 · 2025: 11 · 2024: 12 · 2023: 7 · 2022: 6 · 2021: 6
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Temerty Chair in Focused Ultrasound Research at Sunnybrook Health Sciences Centre
  • Bracco SA, Switzerland
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
Keywords
focused ultrasound, microbubbles, blood-brain barrier permeability, BBB leakage, neuroinflammation, microbubble size distribution, monodisperse microbubbles, Definity, pro-inflammatory gene expression, IL-1β, MCP-1, TNF-α, acoustic feedback control, red blood cell extravasation
MeSH terms
Ultrasonic Waves, Animals, Biological Transport, Blood-Brain Barrier, Brain, Male, Permeability, Sonication, Ultrasonic Therapy, Drug Delivery Systems, Rats, Sprague-Dawley, Microbubbles, Rats

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