期刊
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
卷 69, 期 4, 页码 1359-1368出版社
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TBME.2021.3115553
关键词
Acoustics; Transducers; Mice; Lenses; Ultrasonic imaging; Couplings; Brain modeling; Acoustic holograms; blood-brain barrier; transcranial focused ultrasound
资金
- Spanish Ministry of Science, Innovation, and Universities (MICINN) through Grants Juan de la Cierva -Incorporacion [IJC2018-037897-I, PID2019-111436RB-C22]
- Agencia Valenciana de la Innovacio [INNVAL10/19/016, INNCON/2021/8, INNVA1/2020/92]
- Generalitat Valenciana [ACIF/2017/045, AICO/2020/268, BEFPI/2019/075]
- National Institutes of Health [5R01EB009041, 5R01AG038961]
- European Union through the Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER) of the Comunitat Valenciana [IDIFEDER/2018/022, IDIFEDER/2021/004]
This study demonstrates the feasibility of hologram-assisted blood-brain barrier (BBB) opening for low-cost and highly-localized targeted drug delivery in symmetric regions.
Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS technologies do not allow the simultaneous targeting of several brain structures with high-resolution, and multi-element devices are required to compensate the aberrations introduced by the skull. In this work, we present the first preclinical application of acoustic holograms to perform a bilateral BBB opening in two mirrored regions in mice. The system consisted of a single-element focused transducer working at 1.68 MHz, coupled to a 3D-printed acoustic hologram designed to produce two symmetric foci in anesthetized mice in vivo and, simultaneously, compensate the aberrations of the wavefront caused by the skull bones. T1-weighed MR images showed gadolinium extravasation at two symmetric quasi-spherical focal spots. By encoding time-reversed fields, holograms are capable of focusing acoustic energy with a resolution near the diffraction limit at multiple spots inside the skull of small preclinical animals. This work demonstrates the feasibility of hologram-assisted BBB opening for low-cost and highly-localized targeted drug delivery in the CNS in symmetric regions of separate hemispheres.
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