Histologic Safety of Transcranial Focused Ultrasound Neuromodulation and Magnetic Resonance Acoustic Radiation Force Imaging in Rhesus Macaques and Sheep

Overview

Journal Brain Stimul

Publisher Elsevier

Specialty Neurology

Date 2020 Apr 15

PMID 32289711

Citations 31

Authors

Pooja Gaur

Kerriann M Casey

Jan Kubanek

Ningrui Li

Morteza Mohammadjavadi

Yamil Saenz

Gary H Glover

Donna M Bouley

Kim Butts Pauly

Affiliations

Soon will be listed here.

Abstract

Background: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).

Objective: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.

Methods: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.

Results: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.

Conclusions: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

Citing Articles

Modulating nociception networks: the impact of low-intensity focused ultrasound on thalamocortical connectivity.

Mishra A, Yang P, Manuel T, Newton A, Phipps M, Luo H Brain Commun. 2025; 7(1):fcaf062.

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The future of transcranial ultrasound as a precision brain interface.

Murphy K, Fouragnan E PLoS Biol. 2024; 22(10):e3002884.

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Kusunose J, Rodriguez W, Luo H, Manuel T, Phipps M, Yang P IEEE Trans Ultrason Ferroelectr Freq Control. 2024; 71(8):1030-1041.

PMID: 39024077 PMC: 11465451. DOI: 10.1109/TUFFC.2024.3420242.

Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and Community Resource.

Caffaratti H, Slater B, Shaheen N, Rhone A, Calmus R, Kritikos M medRxiv. 2024; .

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A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound.

Lee K, Park T, Lee W, Kim H Biomed Eng Lett. 2024; 14(3):407-438.

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