The threshold for brain damage in rabbits induced by bursts of ultrasound in the presence of an ultrasound contrast agent (Optison®)
Abstract
The purpose of this study was to test the hypothesis that burst ultrasound (US) in the presence of a US contrast agent using parameters similar to those used in brain blood flow measurements causes tissue damage. The brains of 10 rabbits were sonicated in 3-8 locations with 1.5-MHz, 10- micro s bursts repeated at a frequency of 1 kHz at temporal peak acoustic pressure amplitudes ranging from 2 to 12.7 MPa. The total sonication time for each location was 20 s. Before each sonication, a bolus of US contrast agent was injected IV. Contrast-enhanced magnetic resonance (MR) images were obtained after the sonications to detect local enhancement in the brain. Whole brain histological evaluation was performed, and the sections were stained with hematoxylin and eosin (H and E), TUNEL, and vanadium acid fuchsin (VAF) staining to evaluate tissue effects, including apoptosis and ischemia. Both the magnetic resonance imaging (MRI) contrast enhancement and histology findings indicated that brain tissue damage was induced at a pressure amplitude level of 6.3 MPa. The damage included vascular wall damage, hemorrhage and, eventually, necrosis. Mild vascular damage was observed localized in a few microscopic tissue volumes in about half of the sonicated locations at all pressure values tested (down to 2 MPa). However, these sonications did not induce any detectable tissue effects, including ischemia or apoptosis. As a conclusion, the study showed that the US exposure levels currently used for…
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FUS-MB induces temporary BBB opening even in NHPs.
“A more localized transient disruption of BBB is accomplished by using magnetic resonance imaging-guided focused ultrasound in combination with IV infusion of microbubbles (FUS-MB) (Fig. 4b), which induce temporary BBB opening even in NHPs [134–137].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [136]
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- Authors
- Hynynen, K., McDannold, N., Martin, H., Jolesz, F. A., & Vykhodtseva, N.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Ultrasound in Medicine & Biology
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 29
- Issue
- 3
- Pages
- 473-481
- ISSN
- 0301-5629 (ISSN-L)
- OpenAlex
- W2058265539
- Cited by
- 144
- References
- 31
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 5 · 2013: 7 · 2012: 8
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ultrasound in Medicine & Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA076550, CA76550)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- ultrasound contrast agents, Optison, acoustic pressure threshold, blood-brain barrier opening, vascular wall damage, hemorrhage, necrosis, apoptosis, cerebral ischemia, contrast-enhanced MRI, rabbits
- MeSH terms
- Albumins, Animals, Blood-Brain Barrier, Brain Injuries, Cerebrovascular Circulation, Contrast Media, Fluorocarbons, Magnetic Resonance Imaging, Male, Rabbits, Apoptosis, Ultrasonography, Doppler, Transcranial
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