Robotic device for transcranial focussed ultrasound applications in small animal models

Antoniou, Anastasia; Giannakou, Marinos; Georgiou, Elena; Kleopa, Kleopas A.; Damianou, Christakis

doi:10.1002/rcs.2447

Cited by 6 publications

(1 citation statement)

References 40 publications

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“…FUS was delivered using a manual positioning system [ 29 ] comprising a single element, spherically focused, ultrasound transducer (Piezo Hannas, Wuhan, Hubei, China, 1 MHz central frequency, 80 mm radius of curvature, 50 mm diameter, and 32.5% acoustic efficiency) tuned to an RF amplifier (AG 1016, AG series, T&G Power conversion Inc., Rochester, NY). This system was specially designed to facilitate transcranial FUS studies in rodents.…”

Section: Methodsmentioning

confidence: 99%

FUS-mediated blood–brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice

et al. 2023

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Purpose Amyloid-β (Aβ) peptides, the main component of amyloid plaques found in the Alzheimer's disease (AD) brain, are implicated in its pathogenesis, and are considered a key target in AD therapeutics. We herein propose a reliable strategy for non-invasively delivering a specific anti-Aβ antibody in a mouse model of AD by microbubbles-enhanced Focused Ultrasound (FUS)-mediated Blood–brain barrier disruption (BBBD), using a simple single stage MR-compatible positioning device. Methods The initial experimental work involved wild-type mice and was devoted to selecting the sonication protocol for efficient and safe BBBD. Pulsed FUS was applied using a single-element FUS transducer of 1 MHz (80 mm radius of curvature and 50 mm diameter). The success and extent of BBBD were assessed by Evans Blue extravasation and brain damage by hematoxylin and eosin staining. 5XFAD mice were divided into different subgroups; control (n = 1), FUS + MBs alone (n = 5), antibody alone (n = 5), and FUS + antibody combined (n = 10). The changes in antibody deposition among groups were determined by immunohistochemistry. Results It was confirmed that the antibody could not normally enter the brain parenchyma. A single treatment with MBs-enhanced pulsed FUS using the optimized protocol (1 MHz, 0.5 MPa in-situ pressure, 10 ms bursts, 1% duty factor, 100 s duration) transiently disrupted the BBB allowing for non-invasive antibody delivery to amyloid plaques within the sonicated brain regions. This was consistently reproduced in ten mice. Conclusion These preliminary findings should be confirmed by longer-term studies examining the antibody effects on plaque clearance and cognitive benefit to hold promise for developing disease-modifying anti-Aβ therapeutics for clinical use.

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Section: Methodsmentioning

confidence: 99%

FUS-mediated blood–brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice

et al. 2023

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Robotic device for transcranial focussed ultrasound applications in small animal models

Antoniou

Giannakou

Georgiou

et al. 2022

Robotics Computer Surgery

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Background Focussed Ultrasound (FUS) combined with microbubbles (MBs) was proven a promising modality for non‐invasive blood brain barrier disruption (BBBD). Herein, two devices for FUS‐mediated BBBD in rodents are presented. Methods A two‐axes robotic device was manufactured for navigating a single element FUS transducer of 1 MHz relative to the brain of rodents. A second more compact device featuring a single motorized vertical axis was also developed. Their performance was assessed in terms of motion accuracy, MRI compatibility and trans‐skull BBBD in wild type mice using MBs in synergy with pulsed FUS. Results Successful BBBD was evidenced by the Evans Blue dye method, as well as by Fibronectin and Fibrinogen immunostaining. BBB permeability was enhanced when the applied acoustic intensity was increased. Conclusions The proposed devices constitute a cost‐effective and ergonomic solution for FUS‐mediated BBBD in small animal models. Further experimentation is needed to examine the repeatability of results and optimise the therapeutic protocol.

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Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer

2023

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Purpose The study aims to provide insights on the practicality of using single-element transducers for transcranial Focused Ultrasound (tFUS) thermal applications. Methods FUS sonications were performed through skull phantoms embedding agar-based tissue mimicking gels using a 1 MHz single-element spherically focused transducer. The skull phantoms were 3D printed with Acrylonitrile Butadiene Styrene (ABS) and Resin thermoplastics having the exact skull bone geometry of a healthy volunteer. The temperature field distribution during and after heating was monitored in a 3 T Magnetic Resonance Imaging (MRI) scanner using MR thermometry. The effect of the skull’s thickness on intracranial heating was investigated. Results A single FUS sonication at focal acoustic intensities close to 1580 W/cm2 for 60 s in free field heated up the agar phantom to ablative temperatures reaching about 90 °C (baseline of 37 °C). The ABS skull strongly blocked the ultrasonic waves, resulting in zero temperature increase within the phantom. Considerable heating was achieved through the Resin skull, but it remained at hyperthermia levels. Conversely, tFUS through a 1 mm Resin skull showed enhanced ultrasonic penetration and heating, with the focal temperature reaching 70 °C. Conclusions The ABS skull demonstrated poorer performance in terms of tFUS compared to the Resin skull owing to its higher ultrasonic attenuation and porosity. The thin Resin phantom of 1 mm thickness provided an efficient acoustic window for delivering tFUS and heating up deep phantom areas. The results of such studies could be particularly useful for accelerating the establishment of a wider range of tFUS applications.

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Robotic device for transcranial focussed ultrasound applications in small animal models

Cited by 6 publications

References 40 publications

FUS-mediated blood–brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice

FUS-mediated blood–brain barrier disruption for delivering anti-Aβ antibodies in 5XFAD Alzheimer’s disease mice

Robotic device for transcranial focussed ultrasound applications in small animal models

Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer

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