Feasibility of Hologram-Assisted Bilateral Blood-Brain Barrier Opening in Non-Human Primates
Focused ultrasound (FUS) and microbubbles facilitate blood-brain barrier opening (BBBO) noninvasively, transiently, and safely for targeted drug delivery. Unlike state-of-the-art approaches, in this study, we demonstrate for the first time the simultaneous, bilateral BBBO in non-human primates (NHPs...
| Veröffentlicht in: | IEEE transactions on ultrasonics, ferroelectrics, and frequency control. - 1986. - 71(2024), 10 vom: 02. Okt., Seite 1172-1185 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | IEEE transactions on ultrasonics, ferroelectrics, and frequency control |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural |
| Zusammenfassung: | Focused ultrasound (FUS) and microbubbles facilitate blood-brain barrier opening (BBBO) noninvasively, transiently, and safely for targeted drug delivery. Unlike state-of-the-art approaches, in this study, we demonstrate for the first time the simultaneous, bilateral BBBO in non-human primates (NHPs) using acoustic holograms at caudate and putamen structures. The simple and low-cost system with a single-element FUS transducer and 3-D printed acoustic hologram was guided by neuronavigation and a robotic arm. The advantages of holograms are transcranial aberration correction, simultaneous multifocus and high localization, and target-independent transducer positioning, defining a promising alternative for time- and cost-efficient FUS procedures. Holograms were designed with the k-space method by time-reversal techniques. T1-weighted MRI was used for treatment planning, while the computed tomography (CT) scan provided the head tissues acoustic properties. For the BBBO procedure, a robotic arm allowed transducer positioning errors below 0.1 mm and 0.1°. Following positioning, 0.5-0.6-MPa, 513-kHz microbubble-enhanced FUS was applied for 4 min. For BBBO assessment, Post-FUS T1-weighted MRI was acquired, and contrast enhancement indicated bilateral gadolinium extravasation at both caudate or putamen structures. The two BBBO locations were separated by 13.13 mm with a volume of 91.81 mm3 in the caudate, compared with 9.40 mm with a volume of 124.52 mm3 in simulation, while they were separated by 21.74 mm with a volume of 145.38 mm3 in the putamen and compared with 22.32 mm with a volume of 156.42 mm3 in simulation. No neurological damage was observed through T2-weighted and susceptibility-weighted imaging. This study demonstrates the feasibility and safety of hologram-assisted neuronavigation-guided-FUS for BBBO in NHP, providing thus an avenue for clinical translation |
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| Beschreibung: | Date Completed 10.10.2024 Date Revised 06.01.2025 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1525-8955 |
| DOI: | 10.1109/TUFFC.2024.3451289 |