Robotic Device for Transcranial Focussed Ultrasound Applications in Small Animal Models

Overview

Journal Int J Med Robot

Publisher Wiley

Specialties Biotechnology
General Surgery

Date 2022 Aug 4

PMID 35924335

Authors

Anastasia Antoniou

Marinos Giannakou

Elena Georgiou

Kleopas A Kleopa

Christakis Damianou

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Magnetic Resonance Imaging Monitoring of Thermal Lesions Produced by Focused Ultrasound.

Antoniou A, Evripidou N, Nikolaou A, Georgiou A, Giannakou M, Chrysanthou A J Med Ultrasound. 2025; 32(4):297-308.

PMID: 39801543 PMC: 11717076. DOI: 10.4103/jmu.jmu_112_23.

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

Antoniou A, Evripidou N, Damianou C J Ultrasound. 2023; 27(2):263-274.

PMID: 37517052 PMC: 11178743. DOI: 10.1007/s40477-023-00810-7.

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

Antoniou A, Stavrou M, Evripidou N, Georgiou E, Kousiappa I, Koupparis A J Ultrasound. 2023; 27(2):251-262.

PMID: 37516718 PMC: 11178731. DOI: 10.1007/s40477-023-00805-4.

Robotic device for transcranial focussed ultrasound applications in small animal models.

Antoniou A, Giannakou M, Georgiou E, Kleopa K, Damianou C Int J Med Robot. 2022; 18(6):e2447.

PMID: 35924335 PMC: 9786580. DOI: 10.1002/rcs.2447.

References

Mesiwala A, Farrell L, Wenzel H, Silbergeld D, Crum L, Winn H . High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo. Ultrasound Med Biol. 2002; 28(3):389-400. DOI: 10.1016/s0301-5629(01)00521-x. View

Shou W, Huang X, Duan S, Xia R, Shi Z, Geng X . Acoustic power measurement of high intensity focused ultrasound in medicine based on radiation force. Ultrasonics. 2006; 44 Suppl 1:e17-20. DOI: 10.1016/j.ultras.2006.06.034. View

Burgess A, Ayala-Grosso C, Ganguly M, Jordao J, Aubert I, Hynynen K . Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier. PLoS One. 2011; 6(11):e27877. PMC: 3218061. DOI: 10.1371/journal.pone.0027877. View

Etame A, Diaz R, OReilly M, Smith C, Mainprize T, Hynynen K . Enhanced delivery of gold nanoparticles with therapeutic potential into the brain using MRI-guided focused ultrasound. Nanomedicine. 2012; 8(7):1133-42. PMC: 4101537. DOI: 10.1016/j.nano.2012.02.003. View

McDannold N, Vykhodtseva N, Hynynen K . Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol. 2008; 34(5):834-40. PMC: 2442477. DOI: 10.1016/j.ultrasmedbio.2007.10.016. View

Sheikov N, McDannold N, Vykhodtseva N, Jolesz F, Hynynen K . Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. Ultrasound Med Biol. 2004; 30(7):979-89. DOI: 10.1016/j.ultrasmedbio.2004.04.010. View

Goerner F, Clarke G . Measuring signal-to-noise ratio in partially parallel imaging MRI. Med Phys. 2011; 38(9):5049-57. PMC: 3170395. DOI: 10.1118/1.3618730. View

Thomas G, Khokhlova T, Khokhlova V . Partial Respiratory Motion Compensation for Abdominal Extracorporeal Boiling Histotripsy Treatments With a Robotic Arm. IEEE Trans Ultrason Ferroelectr Freq Control. 2021; 68(9):2861-2870. PMC: 8513721. DOI: 10.1109/TUFFC.2021.3075938. View

Antoniou A, Giannakou M, Georgiou E, Kleopa K, Damianou C . Robotic device for transcranial focussed ultrasound applications in small animal models. Int J Med Robot. 2022; 18(6):e2447. PMC: 9786580. DOI: 10.1002/rcs.2447. View

10.

Antoniou A, Giannakou M, Evripidou N, Stratis S, Pichardo S, Damianou C . Robotic system for top to bottom MRgFUS therapy of multiple cancer types. Int J Med Robot. 2022; 18(2):e2364. DOI: 10.1002/rcs.2364. View

11.

Yang Y, Zhang X, Ye D, Laforest R, Williamson J, Liu Y . Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption. Sci Rep. 2019; 9(1):2840. PMC: 6391404. DOI: 10.1038/s41598-019-39090-9. View

12.

Choi J, Pernot M, Small S, Konofagou E . Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. Ultrasound Med Biol. 2006; 33(1):95-104. DOI: 10.1016/j.ultrasmedbio.2006.07.018. View

13.

Damianou C, Giannakou M, Evripidou N, Kegel S, Huber P, Jenne J . Focused ultrasound robotic system for very small bore magnetic resonance imaging. Int J Med Robot. 2020; 16(6):1-9. PMC: 7816236. DOI: 10.1002/rcs.2165. View

14.

Giannakou M, Drakos T, Menikou G, Evripidou N, Filippou A, Spanoudes K . Magnetic resonance image-guided focused ultrasound robotic system for transrectal prostate cancer therapy. Int J Med Robot. 2021; 17(3):e2237. PMC: 8244034. DOI: 10.1002/rcs.2237. View

15.

Spanoudes K, Evripidou N, Giannakou M, Drakos T, Menikou G, Damianou C . A High Intensity Focused Ultrasound System for Veterinary Oncology Applications. J Med Ultrasound. 2021; 29(3):195-202. PMC: 8515634. DOI: 10.4103/JMU.JMU_130_20. View

16.

Bove T, Zawada T, Serup J, Jessen A, Poli M . High-frequency (20-MHz) high-intensity focused ultrasound (HIFU) system for dermal intervention: Preclinical evaluation in skin equivalents. Skin Res Technol. 2019; 25(2):217-228. DOI: 10.1111/srt.12661. View

17.

Jalali S, Huang Y, Dumont D, Hynynen K . Focused ultrasound-mediated bbb disruption is associated with an increase in activation of AKT: experimental study in rats. BMC Neurol. 2010; 10:114. PMC: 3020671. DOI: 10.1186/1471-2377-10-114. View

18.

Konofagou E . Optimization of the ultrasound-induced blood-brain barrier opening. Theranostics. 2013; 2(12):1223-37. PMC: 3563154. DOI: 10.7150/thno.5576. View

19.

Hynynen K, McDannold N, Sheikov N, Jolesz F, Vykhodtseva N . Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage. 2004; 24(1):12-20. DOI: 10.1016/j.neuroimage.2004.06.046. View

20.

Antoniou A, Giannakou M, Evripidou N, Evripidou G, Spanoudes K, Menikou G . Robotic system for magnetic resonance guided focused ultrasound ablation of abdominal cancer. Int J Med Robot. 2021; 17(5):e2299. DOI: 10.1002/rcs.2299. View