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    Design, characterization and evaluation of a laser-guided focused ultrasound system for preclinical investigations

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    Author
    Anastasiadis, P.
    Mohammadabadi, A.
    Fishman, M.J.
    Date
    2019
    Journal
    BioMedical Engineering Online
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1186/s12938-019-0656-z
    Abstract
    Background: The clinical applications of transcranial focused ultrasound continue to expand and include ablation as well as drug delivery applications in the brain, where treatments are typically guided by MRI. Although MRI-guided focused ultrasound systems are also preferred for many preclinical investigations, they are expensive to purchase and operate, and require the presence of a nearby imaging center. For many basic mechanistic studies, however, MRI is not required. The purpose of this study was to design, construct, characterize and evaluate a portable, custom, laser-guided focused ultrasound system for noninvasive, transcranial treatments in small rodents. Methods: The system comprised an off-the-shelf focused ultrasound transducer and amplifier, with a custom cone fabricated for direct coupling of the transducer to the head region. A laser-guidance apparatus was constructed with a 3D stage for accurate positioning to 1 mm. Pressure field simulations were performed to demonstrate the effects of the coupling cone and the sealing membrane, as well as for determining the location of the focus and acoustic transmission across rat skulls over a range of sizes. Hydrophone measurements and exposures in hydrogels were used to assess the accuracy of the simulations. In vivo treatments were performed in rodents for opening the blood-brain barrier and to assess the performance and accuracy of the system. The effects of varying the acoustic pressure, microbubble dose and animal size were evaluated in terms of efficacy and safety of the treatments. Results: The simulation results were validated by the hydrophone measurements and exposures in the hydrogels. The in vivo treatments demonstrated the ability of the system to open the blood-brain barrier. A higher acoustic pressure was required in larger-sized animals, as predicted by the simulations and transmission measurements. In a particular sized animal, the degree of blood-brain barrier opening, and the safety of the treatments were directly associated with the microbubble dose. Conclusion: The focused ultrasound system that was developed was found to be a cost-effective alternative to MRI-guided systems as an investigational device that is capable of accurately providing noninvasive, transcranial treatments in rodents. Copyright 2019 The Author(s).
    Keyword
    Acoustic transmission
    Blood-brain barrier
    Focused ultrasound
    Hydrogel phantoms
    Hydrophone measurements
    Laser targeting
    Microbubbles
    Microhemorrhage
    Simulations
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063743176&doi=10.1186%2fs12938-019-0656-z&partnerID=40&md5=d1f119c42a9695d469272798c3139141; http://hdl.handle.net/10713/10599
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12938-019-0656-z
    Scopus Count
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