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Multidimensional Safety Assessment of a Low-Intensity Scanning Ultrasound (SUS) Protocol in Sheep
Open accessAbstract
OBJECTIVE: Preclinical studies in mouse models of Alzheimer's disease present low-intensity ultrasound in a scanning mode (SUS) as a promising neuromodulatory modality. However, given the significant differences in brain scale and complexity between mice and humans, we employed sheep as a large animal model to test a novel investigational device and assess safety as a necessary step before deploying SUS in clinical trials. METHODS: Informed by functional assessments in mice, we used image-guided neuro-navigation to deliver a peak negative pressure of 2.6 MPa to four sheep using a scanning approach. Three sheep (#N1-3) underwent a non-recovery procedure followed by histological assessment, and one (#R1) received five repeated treatments spaced out 2-4 weeks over 12 weeks to assess long-term safety via magnetic resonance imaging (MRI) and behavioral observations. RESULTS: In total, 631 sonications were performed, treating up to 50 individual spots per sheep. Evans blue extravasation, and hematoxylin and eosin and vanadium acid fuchsin-toluidine blue staining revealed no evidence of tissue damage or unintended blood-brain barrier (BBB) opening (given no microbubbles were used). Throughout the repeat treatments of sheep #R1, post-operative behavioral observations confirmed normal movement and no signs of pain or distress. MRI revealed no SUS-induced anatomical abnormalities, evidence of BBB opening, microhemorrhages and oedema, in agreement with the histological observations. Mild heating was observed at the inner skull surface following sonication, but no damage to skull or scalp tissue was detected. CONCLUSION: Collectively, the acute and long-term safety assessment of the brain after SUS advocates translation to human studies.
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References 18
Research works printed but not linked: 19
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Metadata
- Authors
- Song, J., Pelekanos, M., Richter-Stretton, G., Leinenga, G., Chicoteau, A., Lee, W., Odabaee, M., Nestor, P. J., Saifzadeh, S., Simon, C., de las Heras, R., & Götz, J.
- Affiliations
- The University of Queensland (AU)
- Queensland University of Technology (AU)
- Corresponding author
- Götz, Jürgen
- ORCID
- Venue
- Ultrasound in Medicine & Biology
- Publisher
- Elsevier BV
- Published
- 2026-09
- Volume
- 52
- Issue
- 9
- Pages
- 2106-2112
- ISSN
- 0301-5629 (ISSN-L)
- OpenAlex
- W7167343634
- Cited by
- 0
- References
- 18
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Ultrasound in Medicine & Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (GNT1176326, GNT2034405)
- Department of Science, Information Technology and Innovation, Queensland Government
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- low-intensity ultrasound, ultrasound neuromodulation, Alzheimer's disease, sheep model, safety assessment, blood-brain barrier integrity, brain tissue damage, microhemorrhages, translational animal model
- MeSH terms
- Animals, Brain, Female, Magnetic Resonance Imaging, Sheep, Sonication, Ultrasonography, Ultrasonic Therapy
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